A Graphical User Interface for BIOEQS: A Program for Simulating and Analyzing Complex Bio-molecular Interactions (original) (raw)

Equilibrium expert: an add-in to Microsoft Excel for multiple binding equilibrium simulations and parameter estimations

Analytical Biochemistry, 2002

An add-in to Microsoft Excel was developed to simulate multiple binding equilibriums. A partition function, readily written even when the equilibrium is complex, describes the experimental system. It involves the concentrations of the different free molecular species and of the different complexes present in the experiment. As a result, the software is not restricted to a series of predefined experimental setups but can handle a large variety of problems involving up to nine independent molecular species. Binding parameters are estimated by nonlinear least-square fitting of experimental measurements as supplied by the user. The fitting process allows user-defined weighting of the experimental data. The flexibility of the software and the way it may be used to describe common experimental situations and to deal with usual problems such as tracer reactivity or nonspecific binding is demonstrated by a few examples. The software is available free of charge upon request.

LiGRO: a graphical user interface for protein-ligand molecular dynamics

Journal of molecular modeling, 2017

To speed up the drug-discovery process, molecular dynamics (MD) calculations performed in GROMACS can be coupled to docking simulations for the post-screening analyses of large compound libraries. This requires generating the topology of the ligands in different software, some basic knowledge of Linux command lines, and a certain familiarity in handling the output files. LiGRO-the python-based graphical interface introduced here-was designed to overcome these protein-ligand parameterization challenges by allowing the graphical (non command line-based) control of GROMACS (MD and analysis), ACPYPE (ligand topology builder) and PLIP (protein-binder interactions monitor)-programs that can be used together to fully perform and analyze the outputs of complex MD simulations (including energy minimization and NVT/NPT equilibration). By allowing the calculation of linear interaction energies in a simple and quick fashion, LiGRO can be used in the drug-discovery pipeline to select compounds w...

ProSim: development of a user-friendly molecular modelling package

2010

We have developed and tested a user-friendly automated molecular modelling workflow with a web-based interface. The workflow has been tested using protein: drug, enzyme: substrate and lectin: sugar interactions. The work presented here involves studies using 3 glycosidases (a human mannosidase, a viral neuraminidase and a protozoan sialidase). We have illustrated the utility of the workflow using the mannosidase and thio-saccharide inhibitor. We have shown the limitations of such in silico technology when working with enzymes like the viral neuraminidase in which dynamic conformation changes take place during the binding or where access to the active site is blocked by a loop or a single residue. The viral neuraminidase inhibitor does not bind to the protozoan sialidase suggesting that such inhibitors would have no use in therapeutic strategies.

Using Molecular Modelling to Study Interactions Between Molecules with Biological Activity

Bioinformatics, 2012

Computational methods have become increasingly important in a number of areas such as comparative or homology modelling, functional site location, characterisation of ligandbinding sites in proteins, docking of small molecules into protein binding sites, proteinprotein docking, and molecular dynamic simulations [see for example Choe & Chang, 2002]. Current results yield information that is sometimes beyond experimental possibilities and can be used to guide and improve a vast array of experiments.

Computational Analyses of Protein-Ligand Interactions

2010

Protein-ligand interactions have a central role in all processes in living systems. A comprehensive understanding of protein interactions with small molecules is of great interest as it provides opportunities for understanding protein function and therapeutic intervention. The major aims of this thesis were to characterise proteinligand interactions from databases of crystal structures and to apply molecular modelling techniques for accurate prediction of binding modes of molecular fragments in protein binding sites. Author's Declaration Chapter 1, 2, 3 in this thesis is my own work. Chapter 4 and 6 were done in collaboration with Dr. Hugues-Olivier Bertrand of Accelrys, who performed docking calculations with GOLD and validated my MCSS calculations by re-running them. Chapter 5 in this thesis is my own work.

Elucidating Protein Binding Mechanisms by Variable- c ITC

ChemBioChem, 2009

Isothermal Titration Calorimetry (ITC) is a powerful method for characterizing the energetics of biological interactions. The approach yields the thermodynamic signature of binding (ΔH, ΔS and K D ) through an analysis of the heat released or absorbed as a ligand is incrementally titrated into a solution of its binding partner. ITC is commonly applied to simple binary complexes, but can also provide important insights into more complicated systems in which ligands bind at multiple sites that are allosterically coupled. 2 Allostery and cooperativity are central to biological regulation, and it is of great interest to elucidate the underlying molecular mechanisms. 3 Studying these systems by ITC remains a significant challenge. 2 For example, a number of different binding models can sometimes provide essentially identical fits to the same data, as is shown to be the case in this study. If the binding mechanism is not known a priori, it can be very difficult to determine which model is correct. Here we report a simple approach for discriminating between different binding mechanisms, based on a global analysis of ITC data obtained over a range of sample concentrations.

Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks

Genome Research, 2003

Cytoscape is an open source software project for integrating biomolecular interaction networks with high-throughput expression data and other molecular states into a unified conceptual framework. Although applicable to any system of molecular components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape's software Core provides basic functionality to layout and query the network; to visually integrate the network with expression profiles, phenotypes, and other molecular states; and to link the network to databases of functional annotations. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of additional computational analyses and features. Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.

CHARMM: The biomolecular simulation program

Journal of Computational Chemistry, 2009

CHARMM (Chemistry at HARvard Molecular Mechanics) is a highly versatile and widely used molecular simulation program. It has been developed over the last three decades with a primary focus on molecules of biological interest, including proteins, peptides, lipids, nucleic acids, carbohydrates, and small molecule ligands, as they occur in solution, crystals, and membrane environments. For the study of such systems, the program provides a large suite of computational tools that include numerous conformational and path sampling methods, free energy estimators, molecular minimization, dynamics, and analysis techniques, and model-building capabilities. The CHARMM program is applicable to problems involving a much broader class of many-particle systems. Calculations with CHARMM can be performed using a number of different energy functions and models, from mixed quantum mechanical-molecular mechanical force fields, to all-atom classical potential energy functions with explicit solvent and various boundary conditions, to implicit solvent and membrane models. The program has been ported to numerous platforms in both serial and parallel architectures. This article provides an overview of the program as it exists today with an emphasis on developments since the publication of the original CHARMM article