Molecular dynamics simulation of protein (original) (raw)
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Molecular Dynamics Simulation of Proteins: A Brief Overview
Journal of Physical Chemistry & Biophysics, 2014
MD simulation has become an essential tool for understanding the physical basis of the structure of proteins and their biological functions. During the current decade we witnessed significant progress in MD simulation of proteins with advancement in atomistic simulation algorithms, force fields, computational methods and facilities, comprehensive analysis and experimental validation, as well as integration in wide area bioinformatics and structural/systems biology frameworks. In this review, we present the methodology on protein simulations and recent advancements in the field. MD simulation provides a platform to study protein-protein, protein-ligand and protein-nucleic acid interactions. MD simulation is also done with NMR relaxation timescale in order to get residual dipolar coupling and order parameter of protein molecules.
Using NMR Chemical Shifts as Structural Restraints in Molecular Dynamics Simulations of Proteins
Structure, 2010
We introduce a procedure to determine the structures of proteins by incorporating NMR chemical shifts as structural restraints in molecular dynamics simulations. In this approach, the chemical shifts are expressed as differentiable functions of the atomic coordinates and used to compute forces to generate trajectories that lead to the reduction of the differences between experimental and calculated chemical shifts. We show that this strategy enables the folding of a set of proteins with representative topologies starting from partially denatured initial conformations without the use of additional experimental information. This method also enables the straightforward combination of chemical shifts with other standard NMR restraints, including those derived from NOE, J-coupling, and residual dipolar coupling measurements. We illustrate this aspect by calculating the structure of a transiently populated excited state conformation from chemical shift and residual dipolar coupling data measured by relaxation dispersion NMR experiments. Structure Molecular Dynamics with Chemical Shift Restraints 924 Structure 18, 923-933, August 11,
Atomic-Resolution Structural Dynamics in Crystalline Proteins from NMR and Molecular Simulation
Solid-state NMR can provide atomic-resolution information about protein motions occurring on a vast range of time scales under similar conditions to those of Xray diffraction studies and therefore offers a highly complementary approach to characterizing the dynamic fluctuations occurring in the crystal. We compare experimentally determined dynamic parameters, spin relaxation, chemical shifts, and dipolar couplings, to values calculated from a 200 ns MD simulation of protein GB1 in its crystalline form, providing insight into the nature of structural dynamics occurring within the crystalline lattice. This simulation allows us to test the accuracy of commonly applied procedures for the interpretation of experimental solid-state relaxation data in terms of dynamic modes and time scales. We discover that the potential complexity of relaxationactive motion can lead to significant under-or overestimation of dynamic amplitudes if different components are not taken into consideration. SECTION: Biophysical Chemistry and Biomolecules
Structure Of Biomolecules Through Molecular Dynamics Simulations
Procedia Computer Science, 2019
Proteins are complex biological macromolecules performing a great variety of functions in the living systems. In order to get insight into the atomic structures and the time evolution of proteins, besides experimental techniques, mathematical and computational modeling approaches can be also used. Nowadays, Molecular Dynamics (MD) simulations constitute a powerful technique for understanding the physical basis of the structure of proteins, since via MD simulations someone can obtain information about proteins at the microscopic level and express it in macroscopic properties. In the current work, we present a detailed simulation approach concerning the modeling of two proteins in the native state, through all-atom Molecular Dynamics simulations under specific (physiological) conditions. The homodimeric Rop protein, that is a paradigm of a canonical 4-a-helical bundle, and its loopless mutation (RM6) are studied in aqueous solution. Their structural, conformational properties, as well as their hydrogen bond network, are characterized in atomic detail. Our findings reveal that both Rop and RM6 proteins have stable native states. The stability of the secondary conformation can be attributed to the formation of hydrogen bonds. The calculation of the root mean square deviation (RMSD) verifies that the system is in an equilibrated structure, validating at the same time, our model. Furthermore, the stereochemical quality of our protein models is demonstrated through the calculation of the Ramachandran plot. Finally, the thermal stability of RM6 protein is studied, and the results show that it is a hyperthermostable protein.
Molecular Dynamics: Survey of Methods for Simulating the Activity of Proteins
Chemical Reviews, 2006
time-dependent (i.e., kinetic) phenomena. This enables an understanding to be developed of various dynamic aspects of biomolecular structure, recognition, and function. However, when used alone, MD is of limited utility. An MD trajectory (i.e., the progress of simulated structure with respect to time) generally provides data only at the level of atomic positions, velocities, and single-point energies. To obtain the macroscopic properties in which one is usually interested requires the application of statistical mechanics, which connects microscopic simulations and macroscopic observables. Statistical mechanics provides a rigorous framework of mathematical expressions that relate the distributions and motions of atoms and molecules to macroscopic observables such as pressure, heat capacity, and free energies. 17,18 Extraction of these macroscopic observables is therefore possible from the microscopic data, and one can predict, for instance, changes in the binding free energy of a particular drug candidate or the mechanisms and energetic consequences of conformational change in a particular protein. Specific aspects of biomolecular structure, kinetics, and thermodynamics that may be investigated via MD include, for example, macromolecular stability, 19 conformational and allosteric properties, 20 the role of dynamics in enzyme activity, 21,22 molecular recognition and the properties of complexes, 21,23 ion and small molecule transport, 24,25 protein association, 26 protein folding, 27,16 and protein hydration. 28 MD, therefore, provides the opportunity to perform a variety of studies including molecular design (drug design 29 and protein design 30) and structure determination and refinement (Xray,31 NMR, 32 and modeling 33). 3. Molecular Dynamics Methods and Theory Given the structure of a biomolecular system, that is, the relative coordinates of the constituent atoms, there are various computational methods that can be used to investigate and study the dynamics of that system. In the present section, a number of such methods are described and discussed. The majority of important dynamics methodologies are highly dependent upon the availability of a suitable potential-energy function to describe the energy landscape of the system with respect to the aforementioned atomic coordinates. This critical aspect is, therefore, introduced first. 3.1. Potential Functions and the Energy Landscape Choice of an appropriate energy function for describing the intermolecular and intramolecular interactions is critical to a successful (i.e., valid yet tractable) molecular dynamics simulation. In conventional MD simulations, the energy function for nonbonded interactions tends to be a simple pairwise additive function (for computational reasons) of nuclear coordinates only. This use of a single nuclear coordinate to represent atoms is justified in terms of the Born-Oppenheimer approximation. 34 For bonded groups of atoms, that is those that form covalent bonds, bond angles, or dihedral angles, simple two-body, three-body, and four-body terms are used, as described below.
Protocol for MM/PBSA Molecular Dynamics Simulations of Proteins
Biophysical Journal, 2003
Continuum solvent models have been employed in past years for understanding processes such as protein folding or biomolecular association. In the last decade, several attempts have been made to merge atomic detail molecular dynamics simulations with solvent continuum models. Among continuum models, the Poisson-Boltzmann solvent accessible surface area model is one of the oldest and most fundamental. Notwithstanding its wide usage for simulation of biomolecular electrostatic potential, the Poisson-Boltzmann equation has been very seldom used to obtain solvation forces for molecular dynamics simulation. We propose here a fast and reliable methodology to implement continuum forces in standard molecular mechanics and dynamics algorithms. Results for a totally unrestrained 1 ns molecular dynamics simulation of a small protein are quantitatively similar to results obtained by explicit solvent molecular dynamics simulations.
Current State-of-the-Art Molecular Dynamics Methods and Applications
Advances in protein chemistry and structural biology, 2014
Molecular dynamics simulations are used to describe the patterns, strength, and properties of protein behavior, drug-receptor interactions, the solvation of molecules, the Advances in Protein Chemistry and Structural Biology, Volume 94 # 2014 Elsevier Inc.
Synergistic use of NMR and MD simulations to study the structural heterogeneity of proteins
Wiley Interdisciplinary Reviews: Computational Molecular Science, 2012
ABSTRACT Nuclear magnetic resonance spectroscopy (NMR) and molecular dynamics (MD) simulations are powerful techniques for the structural characterization of macromolecules. NMR is unique in its ability to provide experimental information at atomic level on the structure as well as on the amplitude and rate of structural fluctuations. MD provides physically sound models and potential mechanisms that connect conformations in time. Nevertheless, none of these techniques allow yet obtaining experimentally validated movies of protein motions at atomic resolution. Instead, it is their complementarity and synergy which offer a unique opportunity toward this end. Here, we overview recent examples that illustrate how much these two techniques benefit from each other, both passively and actively, for the characterization of the structural heterogeneity in proteins. © 2012 John Wiley & Sons, Ltd.
Proteins-structure Function and Bioinformatics, 2001
The latest version of the classical molecular interaction potential (CMIP) has the ability to predict the position of crystallographic waters in several proteins with great accuracy. This article analyzes the ability of the CMIP functional to improve the setup procedure of the molecular system in molecular dynamics (MD) simulations of proteins. To this end, the CMIP strategy is used to include both water molecules and counterions in different protein systems. The structural details of the configurations sampled from trajectories obtained using the CMIP setup procedure are compared with those obtained from trajectories derived from a standard equilibration process. The results show that standard MD simulations can lead to artifactual results, which are avoided using the CMIP setup procedure. Because the CMIP is easy to implement at a low computational cost, it can be very useful in obtaining reliable MD trajectories. Proteins 2001;45:428–437. © 2001 Wiley-Liss, Inc.