Yixiang Cao - Academia.edu (original) (raw)

Papers by Yixiang Cao

Research paper thumbnail of A Polarizable Force Field and Continuum Solvation Methodology for Modeling of Protein−Ligand Interactions

Journal of Chemical Theory and Computation, 2005

A polarizable force field, and associated continuum solvation model, have been developed for the ... more A polarizable force field, and associated continuum solvation model, have been developed for the explicit purpose of computing and studying the energetics and structural features of protein binding to the wide range of ligands with potential for medicinal applications. Parameters for the polarizable force field (PFF) are derived from gas-phase ab initio calculations and then utilized for applications in which the protein binding to ligands occurs in aqueous solvents, wherein the charge distributions of proteins and ligands can be dramatically altered. The continuum solvation model is based on a self-consistent reaction field description of solvation, incorporating an analytical gradient, that allows energy minimizations (and, potentially, molecular dynamics simulations) of protein/ligand systems in continuum solvent. This technology includes a nonpolar model describing the cost of cavity formation, and van der Waals interactions, between the continuum solvent and protein/ligand solutes. Tests of the structural accuracy and computational stability of the methodology, and timings for energy minimizations of proteins and protein/ligand systems in the condensed phase, are reported. In addition, the derivation of polarizability, electrostatic, exchange repulsion, and torsion parameters from ab initio data is described, along with the use of experimental solvation energies for determining parameters for the solvation model.

Research paper thumbnail of Highly efficient implementation of the analytical gradients of pseudospectral time-dependent density functional theory

The Journal of chemical physics, 2021

The accuracy and efficiency of time-dependent density functional theory (TDDFT) excited state gra... more The accuracy and efficiency of time-dependent density functional theory (TDDFT) excited state gradient calculations using the pseudospectral method are presented. TDDFT excited state geometry optimizations of the G2 test set molecules, the organic fluorophores with large Stokes shifts, and the Pt-complexes show that the pseudospectral method gives average errors of 0.01-0.1 kcal/mol for the TDDFT excited state energy, 0.02-0.06 pm for the bond length, and 0.02-0.12° for the bond angle when compared to the results from conventional TDDFT. TDDFT gradient calculations of fullerenes (Cn, n up to 540) with the B3LYP functional and 6-31G** basis set show that the pseudospectral method provides 8- to 14-fold speedups in the total wall clock time over the conventional methods. The pseudospectral TDDFT gradient calculations with a diffuse basis set give higher speedups than the calculations for the same basis set without diffuse functions included.

Research paper thumbnail of Pseudospectral implementations of long‐range corrected density functional theory

Journal of Computational Chemistry

Research paper thumbnail of Accelerated discovery of OLED materials through atomic-scale simulation

Organic Light Emitting Materials and Devices XX, 2016

Research paper thumbnail of Virtual screening and evaluation of highly efficient organometallic light-emitting materials

Organic Light Emitting Materials and Devices XX, 2016

Research paper thumbnail of High performance of the pseudospectral method in modern quantum chemistry

Thesis Columbia University Source Dai B 60 01 P 197 Jul 1999 193 Pages, Jul 1, 1999

Research paper thumbnail of Highly efficient implementation of pseudospectral time-dependent density-functional theory for the calculation of excitation energies of large molecules

Journal of Computational Chemistry, 2016

We have developed and implemented pseudospectral time-dependent density-functional theory (TDDFT)... more We have developed and implemented pseudospectral time-dependent density-functional theory (TDDFT) in the quantum mechanics package Jaguar to calculate restricted singlet and restricted triplet, as well as unrestricted excitation energies with either full linear response (FLR) or the Tamm-Dancoff approximation (TDA) with the pseudospectral length scales, pseudospectral atomic corrections, and pseudospectral multigrid strategy included in the implementations to improve the chemical accuracy and to speed the pseudospectral calculations. The calculations based on pseudospectral time-dependent density-functional theory with full linear response (PS-FLR-TDDFT) and within the Tamm-Dancoff approximation (PS-TDA-TDDFT) for G2 set molecules using B3LYP/6-31G*(*) show mean and maximum absolute deviations of 0.0015 eV and 0.0081 eV, 0.0007 eV and 0.0064 eV, 0.0004 eV and 0.0022 eV for restricted singlet excitation energies, restricted triplet excitation energies, and unrestricted excitation energies, respectively; compared with the results calculated from the conventional spectral method. The application of PS-FLR-TDDFT to OLED molecules and organic dyes, as well as the comparisons for results calculated from PS-FLR-TDDFT and best estimations demonstrate that the accuracy of both PS-FLR-TDDFT and PS-TDA-TDDFT. Calculations for a set of medium-sized molecules, including Cn fullerenes and nanotubes, using the B3LYP functional and 6-31G(**) basis set show PS-TDA-TDDFT provides 19- to 34-fold speedups for Cn fullerenes with 450-1470 basis functions, 11- to 32-fold speedups for nanotubes with 660-3180 basis functions, and 9- to 16-fold speedups for organic molecules with 540-1340 basis functions compared to fully analytic calculations without sacrificing chemical accuracy. The calculations on a set of larger molecules, including the antibiotic drug Ramoplanin, the 46-residue crambin protein, fullerenes up to C540 and nanotubes up to 14×(6,6), using the B3LYP functional and 6-31G(**) basis set with up to 8100 basis functions show that PS-FLR-TDDFT CPU time scales as N(2.05) with the number of basis functions. © 2016 Wiley Periodicals, Inc.

Research paper thumbnail of Virtual screening for OLED materials

Organic Light Emitting Materials and Devices XVIII, 2014

Research paper thumbnail of Correlated ab Initio Electronic Structure Calculations for Large Molecules

The Journal of Physical Chemistry A, 1999

ABSTRACT We discuss computational methods for carrying out correlated ab initio electronic struct... more ABSTRACT We discuss computational methods for carrying out correlated ab initio electronic structure calculations for large systems. The focus is on two types of methods: density functional theory (DFT) and localized orbital methods such as local MP2 (LMP2) and a multireference version based upon a generalized valence bond reference wave function, GVB-LMP2. The computational performance of both approaches using pseudospectral numerical methods is documented, and calculated thermochemical and conformational energetics are compared to experimental data.

Research paper thumbnail of The VSGB 2.0 model: A next generation energy model for high resolution protein structure modeling

Proteins: Structure, Function, and Bioinformatics, 2011

A novel energy model (VSGB 2.0) for high resolution protein structure modeling is described, whic... more A novel energy model (VSGB 2.0) for high resolution protein structure modeling is described, which features an optimized implicit solvent model as well as physics-based corrections for hydrogen bonding, π-π interactions, self-contact interactions, and hydrophobic interactions. Parameters of the VSGB 2.0 model were fit to a crystallographic database of 2239 single side chain and 100 11-13 residue loop predictions. Combined with an advanced method of sampling and a robust algorithm for protonation state assignment, the VSGB 2.0 model was validated by predicting 115 super long loops up to 20 residues. Despite the dramatically increasing difficulty in reconstructing longer loops, a high accuracy was achieved: all of the lowest energy conformations have global backbone RMSDs better than 2.0 Å from the native conformations. Average global backbone RMSDs of the predictions are 0.51, 0.63, 0.70, 0.62, 0.80, 1.41, and 1.59 Å for 14, 15, 16, 17, 18, 19, and 20 residue loop predictions, respectively. When these results are corrected for possible statistical bias as explained in the text, the average global backbone RMSDs are 0.61, 0.71, 0.86, 0.62, 1.06, 1.67, and 1.59 Å. Given the precision and robustness of the calculations, we believe that the VSGB 2.0 model is suitable to tackle "real" problems, such as biological function modeling and structure-based drug discovery.

Research paper thumbnail of High-throughput quantum chemistry and virtual screening for lithium ion battery electrolyte additives

Journal of Power Sources, 2010

ABSTRACT Advances in the stability and efficiency of electronic structure codes along with the in... more ABSTRACT Advances in the stability and efficiency of electronic structure codes along with the increased performance of commodity computing resources has enabled the automated high-throughput quantum chemical analysis of materials structure libraries containing thousands of structures. This allows the computational screening of a materials design space to identify lead systems and estimate critical structure–property limits which should prove an invaluable tool in informing experimental discovery and development efforts. Here this approach is illustrated for lithium ion battery additives. An additive library consisting of 7381 structures was generated, based on fluoro- and alkyl-derivatized ethylene carbonate (EC). Molecular properties (e.g. LUMO, EA, μ and η) were computed for each structure using the PM3 semiempirical method. The resulting lithium battery additive library was then analyzed and screened to determine the suitability of the additives, based on properties correlated with performance as a reductive additive for battery electrolyte formulations.

Research paper thumbnail of Development of a polarizable force field for proteins via ab initio quantum chemistry: First generation model and gas phase tests

Journal of Computational Chemistry, 2002

We present results of developing a methodology suitable for producing molecular mechanics force f... more We present results of developing a methodology suitable for producing molecular mechanics force fields with explicit treatment of electrostatic polarization for proteins and other molecular system of biological interest. The technique allows simulation of realistic-size systems. Employing highlevel ab initio data as a target for fitting allows us to avoid the problem of the lack of detailed experimental data. Using the fast and reliable quantum mechanical methods supplies robust fitting data for the resulting parameter sets. As a result, gas-phase many-body effects for dipeptides are captured within the average RMSD of 0.22 kcal/mol from their ab initio values, and conformational energies for the di-and tetrapeptides are reproduced within the average RMSD of 0.43 kcal/mol from their quantum mechanical counterparts. The latter is achieved in part because of application of a novel torsional fitting technique recently developed in our group, which has already been used to greatly improve accuracy of the peptide conformational equilibrium prediction with the OPLS-AA force field. 1 Finally, we have employed the newly developed firstgeneration model in computing gas-phase conformations of real proteins, as well as in molecular dynamics studies of the systems. The results show that, although the overall accuracy is no better than what can be achieved with a fixed-charges model, the methodology produces robust results, permits reasonably low computational cost, and avoids other computational problems typical for polarizable force fields. It can be considered as a solid basis for building a more accurate and complete second-generation model.

Research paper thumbnail of Efficient pseudospectral methods for density functional calculations

The Journal of Chemical Physics, 2000

ABSTRACT Novel improvements of the pseudospectral method for assembling the Coulomb operator are ... more ABSTRACT Novel improvements of the pseudospectral method for assembling the Coulomb operator are discussed. These improvements consist of a fast atom centered multipole method and a variation of the Head–Gordan J-engine analytic integral evaluation. The details of the methodology are discussed and performance evaluations presented for larger molecules within the context of DFT energy and gradient calculations. © 2000 American Institute of Physics.

Research paper thumbnail of Nuclear-magnetic-resonance shielding constants calculated by pseudospectral methods

The Journal of Chemical Physics, 2005

We have developed an algorithm based upon pseudospectral (PS) ab initio electronic structure meth... more We have developed an algorithm based upon pseudospectral (PS) ab initio electronic structure methods for evaluating nuclear magnetic shielding constants using gauge-including atomic orbitals (GIAOs) in the spin-restricted and spin-unrestricted formalisms of Hartree-Fock (HF) theory and density-functional theory (DFT). The nuclear magnetic shielding constants for both 1H and 13C calculated using PS methodology for 21 small molecules have absolute mean errors of less than 0.3 ppm in comparison with analytic integral results. CPU timing comparisons between PS methods and conventional methods carried out for seven large molecules ranging from 510 to 1285 basis functions demonstrate that the PS methods are an order of magnitude more efficient than the conventional methods. PS-HF was between 9 and 26 times faster than conventional integral technology, and PS-DFT (Becke three-parameter Lee-Yang-Parr) was between 6 and 21 times faster.

Research paper thumbnail of Molecular (hyper)polarizabilities computed by pseudospectral methods

The Journal of Chemical Physics, 2005

We have developed algorithms based on pseudospectral (PS) ab initio electronic structure methods ... more We have developed algorithms based on pseudospectral (PS) ab initio electronic structure methods for solving the first- and second-order Hartree-Fock/Kohn-Sham equations and evaluating molecular polarizabilities and first- and second-order hyperpolarizabilities in the spin-restricted and spin-unrestricted formalisms at the Hartree-Fock (HF) and density functional theory (DFT) levels. We carry out calculations on 50 small molecules to test the accuracy of the PS approach. Our results demonstrate that the molecular polarizability alpha computed by the PS method is essentially identical to the value obtained from conventional methods for both HF and DFT calculations, while the first-order hyperpolarizability beta and second-order hyperpolarizability gamma have mean unsigned percentage differences of 1.26% and 0.62% (HF) and 0.78% and 0.65% (DFT), respectively. We also present CPU timing comparisons between the PS and conventional methods at the 6-31 G(**) level for 14 molecules having 185 to 1185 basis functions. The timing results show that the PS method is 25 (PS-HF) and 13 (PS-DFT) times faster than the conventional method for a system with 500 basis functions. The PS methods are found scale as N(2.70) (PS-HF) and N(2.40) (PS-DFT), while the conventional methods scale as N(2.93) (PRISM-HF) and N(2.87) (PRISM-DFT), where N is the number of basis functions.

Research paper thumbnail of A localized orbital analysis of the thermochemical errors in hybrid density functional theory: Achieving chemical accuracy via a simple empirical correction scheme

The Journal of Chemical Physics, 2006

This paper describes an empirical localized orbital correction model which improves the accuracy ... more This paper describes an empirical localized orbital correction model which improves the accuracy of density functional theory (DFT) methods for the prediction of thermochemical properties for molecules of first and second row elements. The B3LYP localized orbital correction version of the model improves B3LYP DFT atomization energy calculations on the G3 data set of 222 molecules from a mean absolute deviation (MAD) from experiment of 4.8 to 0.8 kcal/mol. The almost complete elimination of large outliers and the substantial reduction in MAD yield overall results comparable to the G3 wave-function-based method; furthermore, the new model has zero additional computational cost beyond standard DFT calculations. The following four classes of correction parameters are applied to a molecule based on standard valence bond assignments: corrections to atoms, corrections to individual bonds, corrections for neighboring bonds of a given bond, and radical environmental corrections. Although the model is heuristic and is based on a 22 parameter multiple linear regression to experimental errors, each of the parameters is justified on physical grounds, and each provides insight into the fundamental limitations of DFT, most importantly the failure of current DFT methods to accurately account for nondynamical electron correlation.

Research paper thumbnail of Ab initio predictions of large hyperpolarizability push-pull polymers. Julolidinyl-n-isoxazolone and julolidinyl-n-N,N′-diethylthiobarbituric acid

Chemical Physics Letters, 1995

Recently significant advances have been made in engineering push-pull organic chromophores to hav... more Recently significant advances have been made in engineering push-pull organic chromophores to have very large hyperpolarizabilities ( β ), leading to materials with μβ as high as 15000 X 10−48 esu. Such developments have been slow and costy because of difficulties in synthesis, purification, and measurement. As an alternative we have developed a new quantum mechanical program (PS-GVB/NLO) which provides predictions of β for such molecules far faster preeviously possible. We have applied PS-GVB/NLO to predicting a, β, and γ for the high β push-pull organics and find excellent agreement with experiment. This suggests that theory can be used as an effective tool for developing new nonlinear optical materials.

Research paper thumbnail of Large-Scale ab Initio Quantum Chemical Calculations on Biological Systems

Accounts of Chemical Research, 2001

In this Account we describe recent advances in two ab initio electronic structure methods, locali... more In this Account we describe recent advances in two ab initio electronic structure methods, localized perturbation approaches and density functional theory, that allow accurate calculations including electron correlation to be carried out for systems with hundreds of atoms. Application of these methods to large-scale modeling of biological systems is discussed. Localized perturbation methods are best suited to computation of conformational energetics and nonbonded interactions: determination of the relative energetics of various conformations of the alanine tetrapetide is presented. Density functional theory is the method of choice for studying reactive chemistry; investigations of the catalytic cycle of the enzyme methane monooxygenase are reviewed.

Research paper thumbnail of Integrated modeling program, applied chemical theory (IMPACT)

We provide an overview of the IMPACT molecular mechanics program with an emphasis on recent devel... more We provide an overview of the IMPACT molecular mechanics program with an emphasis on recent developments and a description of its current functionality. With respect to core molecular mechanics technologies we include a status report for the fixed charge and polarizable force fields that can be used with the program and illustrate how the force fields, when used together with new atom typing and parameter assignment modules, have greatly expanded the coverage of organic compounds and medicinally relevant ligands. As we discuss in this review, explicit solvent simulations have been used to guide our design of implicit solvent models based on the generalized Born framework and a novel nonpolar estimator that have recently been incorporated into the program. With IMPACT it is possible to use several different advanced conformational sampling algorithms based on combining features of molecular dynamics and Monte Carlo simulations. The program includes two specialized molecular mechanics modules: Glide, a high-throughput docking program, and QSite, a mixed quantum mechanics/molecular mechanics module. These modules employ the IMPACT infrastructure as a starting point for the construction of the protein model and assignment of molecular mechanics parameters, but have then been developed to meet specialized objectives with respect to sampling and the energy function.

Research paper thumbnail of A Polarizable Force Field and Continuum Solvation Methodology for Modeling of Protein−Ligand Interactions

Journal of Chemical Theory and Computation, 2005

A polarizable force field, and associated continuum solvation model, have been developed for the ... more A polarizable force field, and associated continuum solvation model, have been developed for the explicit purpose of computing and studying the energetics and structural features of protein binding to the wide range of ligands with potential for medicinal applications. Parameters for the polarizable force field (PFF) are derived from gas-phase ab initio calculations and then utilized for applications in which the protein binding to ligands occurs in aqueous solvents, wherein the charge distributions of proteins and ligands can be dramatically altered. The continuum solvation model is based on a self-consistent reaction field description of solvation, incorporating an analytical gradient, that allows energy minimizations (and, potentially, molecular dynamics simulations) of protein/ligand systems in continuum solvent. This technology includes a nonpolar model describing the cost of cavity formation, and van der Waals interactions, between the continuum solvent and protein/ligand solutes. Tests of the structural accuracy and computational stability of the methodology, and timings for energy minimizations of proteins and protein/ligand systems in the condensed phase, are reported. In addition, the derivation of polarizability, electrostatic, exchange repulsion, and torsion parameters from ab initio data is described, along with the use of experimental solvation energies for determining parameters for the solvation model.

Research paper thumbnail of A Polarizable Force Field and Continuum Solvation Methodology for Modeling of Protein−Ligand Interactions

Journal of Chemical Theory and Computation, 2005

A polarizable force field, and associated continuum solvation model, have been developed for the ... more A polarizable force field, and associated continuum solvation model, have been developed for the explicit purpose of computing and studying the energetics and structural features of protein binding to the wide range of ligands with potential for medicinal applications. Parameters for the polarizable force field (PFF) are derived from gas-phase ab initio calculations and then utilized for applications in which the protein binding to ligands occurs in aqueous solvents, wherein the charge distributions of proteins and ligands can be dramatically altered. The continuum solvation model is based on a self-consistent reaction field description of solvation, incorporating an analytical gradient, that allows energy minimizations (and, potentially, molecular dynamics simulations) of protein/ligand systems in continuum solvent. This technology includes a nonpolar model describing the cost of cavity formation, and van der Waals interactions, between the continuum solvent and protein/ligand solutes. Tests of the structural accuracy and computational stability of the methodology, and timings for energy minimizations of proteins and protein/ligand systems in the condensed phase, are reported. In addition, the derivation of polarizability, electrostatic, exchange repulsion, and torsion parameters from ab initio data is described, along with the use of experimental solvation energies for determining parameters for the solvation model.

Research paper thumbnail of Highly efficient implementation of the analytical gradients of pseudospectral time-dependent density functional theory

The Journal of chemical physics, 2021

The accuracy and efficiency of time-dependent density functional theory (TDDFT) excited state gra... more The accuracy and efficiency of time-dependent density functional theory (TDDFT) excited state gradient calculations using the pseudospectral method are presented. TDDFT excited state geometry optimizations of the G2 test set molecules, the organic fluorophores with large Stokes shifts, and the Pt-complexes show that the pseudospectral method gives average errors of 0.01-0.1 kcal/mol for the TDDFT excited state energy, 0.02-0.06 pm for the bond length, and 0.02-0.12° for the bond angle when compared to the results from conventional TDDFT. TDDFT gradient calculations of fullerenes (Cn, n up to 540) with the B3LYP functional and 6-31G** basis set show that the pseudospectral method provides 8- to 14-fold speedups in the total wall clock time over the conventional methods. The pseudospectral TDDFT gradient calculations with a diffuse basis set give higher speedups than the calculations for the same basis set without diffuse functions included.

Research paper thumbnail of Pseudospectral implementations of long‐range corrected density functional theory

Journal of Computational Chemistry

Research paper thumbnail of Accelerated discovery of OLED materials through atomic-scale simulation

Organic Light Emitting Materials and Devices XX, 2016

Research paper thumbnail of Virtual screening and evaluation of highly efficient organometallic light-emitting materials

Organic Light Emitting Materials and Devices XX, 2016

Research paper thumbnail of High performance of the pseudospectral method in modern quantum chemistry

Thesis Columbia University Source Dai B 60 01 P 197 Jul 1999 193 Pages, Jul 1, 1999

Research paper thumbnail of Highly efficient implementation of pseudospectral time-dependent density-functional theory for the calculation of excitation energies of large molecules

Journal of Computational Chemistry, 2016

We have developed and implemented pseudospectral time-dependent density-functional theory (TDDFT)... more We have developed and implemented pseudospectral time-dependent density-functional theory (TDDFT) in the quantum mechanics package Jaguar to calculate restricted singlet and restricted triplet, as well as unrestricted excitation energies with either full linear response (FLR) or the Tamm-Dancoff approximation (TDA) with the pseudospectral length scales, pseudospectral atomic corrections, and pseudospectral multigrid strategy included in the implementations to improve the chemical accuracy and to speed the pseudospectral calculations. The calculations based on pseudospectral time-dependent density-functional theory with full linear response (PS-FLR-TDDFT) and within the Tamm-Dancoff approximation (PS-TDA-TDDFT) for G2 set molecules using B3LYP/6-31G*(*) show mean and maximum absolute deviations of 0.0015 eV and 0.0081 eV, 0.0007 eV and 0.0064 eV, 0.0004 eV and 0.0022 eV for restricted singlet excitation energies, restricted triplet excitation energies, and unrestricted excitation energies, respectively; compared with the results calculated from the conventional spectral method. The application of PS-FLR-TDDFT to OLED molecules and organic dyes, as well as the comparisons for results calculated from PS-FLR-TDDFT and best estimations demonstrate that the accuracy of both PS-FLR-TDDFT and PS-TDA-TDDFT. Calculations for a set of medium-sized molecules, including Cn fullerenes and nanotubes, using the B3LYP functional and 6-31G(**) basis set show PS-TDA-TDDFT provides 19- to 34-fold speedups for Cn fullerenes with 450-1470 basis functions, 11- to 32-fold speedups for nanotubes with 660-3180 basis functions, and 9- to 16-fold speedups for organic molecules with 540-1340 basis functions compared to fully analytic calculations without sacrificing chemical accuracy. The calculations on a set of larger molecules, including the antibiotic drug Ramoplanin, the 46-residue crambin protein, fullerenes up to C540 and nanotubes up to 14×(6,6), using the B3LYP functional and 6-31G(**) basis set with up to 8100 basis functions show that PS-FLR-TDDFT CPU time scales as N(2.05) with the number of basis functions. © 2016 Wiley Periodicals, Inc.

Research paper thumbnail of Virtual screening for OLED materials

Organic Light Emitting Materials and Devices XVIII, 2014

Research paper thumbnail of Correlated ab Initio Electronic Structure Calculations for Large Molecules

The Journal of Physical Chemistry A, 1999

ABSTRACT We discuss computational methods for carrying out correlated ab initio electronic struct... more ABSTRACT We discuss computational methods for carrying out correlated ab initio electronic structure calculations for large systems. The focus is on two types of methods: density functional theory (DFT) and localized orbital methods such as local MP2 (LMP2) and a multireference version based upon a generalized valence bond reference wave function, GVB-LMP2. The computational performance of both approaches using pseudospectral numerical methods is documented, and calculated thermochemical and conformational energetics are compared to experimental data.

Research paper thumbnail of The VSGB 2.0 model: A next generation energy model for high resolution protein structure modeling

Proteins: Structure, Function, and Bioinformatics, 2011

A novel energy model (VSGB 2.0) for high resolution protein structure modeling is described, whic... more A novel energy model (VSGB 2.0) for high resolution protein structure modeling is described, which features an optimized implicit solvent model as well as physics-based corrections for hydrogen bonding, π-π interactions, self-contact interactions, and hydrophobic interactions. Parameters of the VSGB 2.0 model were fit to a crystallographic database of 2239 single side chain and 100 11-13 residue loop predictions. Combined with an advanced method of sampling and a robust algorithm for protonation state assignment, the VSGB 2.0 model was validated by predicting 115 super long loops up to 20 residues. Despite the dramatically increasing difficulty in reconstructing longer loops, a high accuracy was achieved: all of the lowest energy conformations have global backbone RMSDs better than 2.0 Å from the native conformations. Average global backbone RMSDs of the predictions are 0.51, 0.63, 0.70, 0.62, 0.80, 1.41, and 1.59 Å for 14, 15, 16, 17, 18, 19, and 20 residue loop predictions, respectively. When these results are corrected for possible statistical bias as explained in the text, the average global backbone RMSDs are 0.61, 0.71, 0.86, 0.62, 1.06, 1.67, and 1.59 Å. Given the precision and robustness of the calculations, we believe that the VSGB 2.0 model is suitable to tackle "real" problems, such as biological function modeling and structure-based drug discovery.

Research paper thumbnail of High-throughput quantum chemistry and virtual screening for lithium ion battery electrolyte additives

Journal of Power Sources, 2010

ABSTRACT Advances in the stability and efficiency of electronic structure codes along with the in... more ABSTRACT Advances in the stability and efficiency of electronic structure codes along with the increased performance of commodity computing resources has enabled the automated high-throughput quantum chemical analysis of materials structure libraries containing thousands of structures. This allows the computational screening of a materials design space to identify lead systems and estimate critical structure–property limits which should prove an invaluable tool in informing experimental discovery and development efforts. Here this approach is illustrated for lithium ion battery additives. An additive library consisting of 7381 structures was generated, based on fluoro- and alkyl-derivatized ethylene carbonate (EC). Molecular properties (e.g. LUMO, EA, μ and η) were computed for each structure using the PM3 semiempirical method. The resulting lithium battery additive library was then analyzed and screened to determine the suitability of the additives, based on properties correlated with performance as a reductive additive for battery electrolyte formulations.

Research paper thumbnail of Development of a polarizable force field for proteins via ab initio quantum chemistry: First generation model and gas phase tests

Journal of Computational Chemistry, 2002

We present results of developing a methodology suitable for producing molecular mechanics force f... more We present results of developing a methodology suitable for producing molecular mechanics force fields with explicit treatment of electrostatic polarization for proteins and other molecular system of biological interest. The technique allows simulation of realistic-size systems. Employing highlevel ab initio data as a target for fitting allows us to avoid the problem of the lack of detailed experimental data. Using the fast and reliable quantum mechanical methods supplies robust fitting data for the resulting parameter sets. As a result, gas-phase many-body effects for dipeptides are captured within the average RMSD of 0.22 kcal/mol from their ab initio values, and conformational energies for the di-and tetrapeptides are reproduced within the average RMSD of 0.43 kcal/mol from their quantum mechanical counterparts. The latter is achieved in part because of application of a novel torsional fitting technique recently developed in our group, which has already been used to greatly improve accuracy of the peptide conformational equilibrium prediction with the OPLS-AA force field. 1 Finally, we have employed the newly developed firstgeneration model in computing gas-phase conformations of real proteins, as well as in molecular dynamics studies of the systems. The results show that, although the overall accuracy is no better than what can be achieved with a fixed-charges model, the methodology produces robust results, permits reasonably low computational cost, and avoids other computational problems typical for polarizable force fields. It can be considered as a solid basis for building a more accurate and complete second-generation model.

Research paper thumbnail of Efficient pseudospectral methods for density functional calculations

The Journal of Chemical Physics, 2000

ABSTRACT Novel improvements of the pseudospectral method for assembling the Coulomb operator are ... more ABSTRACT Novel improvements of the pseudospectral method for assembling the Coulomb operator are discussed. These improvements consist of a fast atom centered multipole method and a variation of the Head–Gordan J-engine analytic integral evaluation. The details of the methodology are discussed and performance evaluations presented for larger molecules within the context of DFT energy and gradient calculations. © 2000 American Institute of Physics.

Research paper thumbnail of Nuclear-magnetic-resonance shielding constants calculated by pseudospectral methods

The Journal of Chemical Physics, 2005

We have developed an algorithm based upon pseudospectral (PS) ab initio electronic structure meth... more We have developed an algorithm based upon pseudospectral (PS) ab initio electronic structure methods for evaluating nuclear magnetic shielding constants using gauge-including atomic orbitals (GIAOs) in the spin-restricted and spin-unrestricted formalisms of Hartree-Fock (HF) theory and density-functional theory (DFT). The nuclear magnetic shielding constants for both 1H and 13C calculated using PS methodology for 21 small molecules have absolute mean errors of less than 0.3 ppm in comparison with analytic integral results. CPU timing comparisons between PS methods and conventional methods carried out for seven large molecules ranging from 510 to 1285 basis functions demonstrate that the PS methods are an order of magnitude more efficient than the conventional methods. PS-HF was between 9 and 26 times faster than conventional integral technology, and PS-DFT (Becke three-parameter Lee-Yang-Parr) was between 6 and 21 times faster.

Research paper thumbnail of Molecular (hyper)polarizabilities computed by pseudospectral methods

The Journal of Chemical Physics, 2005

We have developed algorithms based on pseudospectral (PS) ab initio electronic structure methods ... more We have developed algorithms based on pseudospectral (PS) ab initio electronic structure methods for solving the first- and second-order Hartree-Fock/Kohn-Sham equations and evaluating molecular polarizabilities and first- and second-order hyperpolarizabilities in the spin-restricted and spin-unrestricted formalisms at the Hartree-Fock (HF) and density functional theory (DFT) levels. We carry out calculations on 50 small molecules to test the accuracy of the PS approach. Our results demonstrate that the molecular polarizability alpha computed by the PS method is essentially identical to the value obtained from conventional methods for both HF and DFT calculations, while the first-order hyperpolarizability beta and second-order hyperpolarizability gamma have mean unsigned percentage differences of 1.26% and 0.62% (HF) and 0.78% and 0.65% (DFT), respectively. We also present CPU timing comparisons between the PS and conventional methods at the 6-31 G(**) level for 14 molecules having 185 to 1185 basis functions. The timing results show that the PS method is 25 (PS-HF) and 13 (PS-DFT) times faster than the conventional method for a system with 500 basis functions. The PS methods are found scale as N(2.70) (PS-HF) and N(2.40) (PS-DFT), while the conventional methods scale as N(2.93) (PRISM-HF) and N(2.87) (PRISM-DFT), where N is the number of basis functions.

Research paper thumbnail of A localized orbital analysis of the thermochemical errors in hybrid density functional theory: Achieving chemical accuracy via a simple empirical correction scheme

The Journal of Chemical Physics, 2006

This paper describes an empirical localized orbital correction model which improves the accuracy ... more This paper describes an empirical localized orbital correction model which improves the accuracy of density functional theory (DFT) methods for the prediction of thermochemical properties for molecules of first and second row elements. The B3LYP localized orbital correction version of the model improves B3LYP DFT atomization energy calculations on the G3 data set of 222 molecules from a mean absolute deviation (MAD) from experiment of 4.8 to 0.8 kcal/mol. The almost complete elimination of large outliers and the substantial reduction in MAD yield overall results comparable to the G3 wave-function-based method; furthermore, the new model has zero additional computational cost beyond standard DFT calculations. The following four classes of correction parameters are applied to a molecule based on standard valence bond assignments: corrections to atoms, corrections to individual bonds, corrections for neighboring bonds of a given bond, and radical environmental corrections. Although the model is heuristic and is based on a 22 parameter multiple linear regression to experimental errors, each of the parameters is justified on physical grounds, and each provides insight into the fundamental limitations of DFT, most importantly the failure of current DFT methods to accurately account for nondynamical electron correlation.

Research paper thumbnail of Ab initio predictions of large hyperpolarizability push-pull polymers. Julolidinyl-n-isoxazolone and julolidinyl-n-N,N′-diethylthiobarbituric acid

Chemical Physics Letters, 1995

Recently significant advances have been made in engineering push-pull organic chromophores to hav... more Recently significant advances have been made in engineering push-pull organic chromophores to have very large hyperpolarizabilities ( β ), leading to materials with μβ as high as 15000 X 10−48 esu. Such developments have been slow and costy because of difficulties in synthesis, purification, and measurement. As an alternative we have developed a new quantum mechanical program (PS-GVB/NLO) which provides predictions of β for such molecules far faster preeviously possible. We have applied PS-GVB/NLO to predicting a, β, and γ for the high β push-pull organics and find excellent agreement with experiment. This suggests that theory can be used as an effective tool for developing new nonlinear optical materials.

Research paper thumbnail of Large-Scale ab Initio Quantum Chemical Calculations on Biological Systems

Accounts of Chemical Research, 2001

In this Account we describe recent advances in two ab initio electronic structure methods, locali... more In this Account we describe recent advances in two ab initio electronic structure methods, localized perturbation approaches and density functional theory, that allow accurate calculations including electron correlation to be carried out for systems with hundreds of atoms. Application of these methods to large-scale modeling of biological systems is discussed. Localized perturbation methods are best suited to computation of conformational energetics and nonbonded interactions: determination of the relative energetics of various conformations of the alanine tetrapetide is presented. Density functional theory is the method of choice for studying reactive chemistry; investigations of the catalytic cycle of the enzyme methane monooxygenase are reviewed.

Research paper thumbnail of Integrated modeling program, applied chemical theory (IMPACT)

We provide an overview of the IMPACT molecular mechanics program with an emphasis on recent devel... more We provide an overview of the IMPACT molecular mechanics program with an emphasis on recent developments and a description of its current functionality. With respect to core molecular mechanics technologies we include a status report for the fixed charge and polarizable force fields that can be used with the program and illustrate how the force fields, when used together with new atom typing and parameter assignment modules, have greatly expanded the coverage of organic compounds and medicinally relevant ligands. As we discuss in this review, explicit solvent simulations have been used to guide our design of implicit solvent models based on the generalized Born framework and a novel nonpolar estimator that have recently been incorporated into the program. With IMPACT it is possible to use several different advanced conformational sampling algorithms based on combining features of molecular dynamics and Monte Carlo simulations. The program includes two specialized molecular mechanics modules: Glide, a high-throughput docking program, and QSite, a mixed quantum mechanics/molecular mechanics module. These modules employ the IMPACT infrastructure as a starting point for the construction of the protein model and assignment of molecular mechanics parameters, but have then been developed to meet specialized objectives with respect to sampling and the energy function.

Research paper thumbnail of A Polarizable Force Field and Continuum Solvation Methodology for Modeling of Protein−Ligand Interactions

Journal of Chemical Theory and Computation, 2005

A polarizable force field, and associated continuum solvation model, have been developed for the ... more A polarizable force field, and associated continuum solvation model, have been developed for the explicit purpose of computing and studying the energetics and structural features of protein binding to the wide range of ligands with potential for medicinal applications. Parameters for the polarizable force field (PFF) are derived from gas-phase ab initio calculations and then utilized for applications in which the protein binding to ligands occurs in aqueous solvents, wherein the charge distributions of proteins and ligands can be dramatically altered. The continuum solvation model is based on a self-consistent reaction field description of solvation, incorporating an analytical gradient, that allows energy minimizations (and, potentially, molecular dynamics simulations) of protein/ligand systems in continuum solvent. This technology includes a nonpolar model describing the cost of cavity formation, and van der Waals interactions, between the continuum solvent and protein/ligand solutes. Tests of the structural accuracy and computational stability of the methodology, and timings for energy minimizations of proteins and protein/ligand systems in the condensed phase, are reported. In addition, the derivation of polarizability, electrostatic, exchange repulsion, and torsion parameters from ab initio data is described, along with the use of experimental solvation energies for determining parameters for the solvation model.