Ligand Affinities within the Open-Boundary Molecular Mechanics/Coarse-Grained Framework (I): Alchemical Transformations within the Hamiltonian Adaptive Resolution Scheme

A coarse-grained cellular automaton is proposed to simulate traffic systems. There, cells represent road sections. A cell can be in two states: jammed or passable. Numerical calculations are performed for a piece of square lattice with open boundary conditions, for the same piece with some cells removed and for a map of a small city. The results indicate the presence of a phase transition in the parameter space, between two macroscopic phases: passable and jammed. The results are supplemented by exact calculations of the stationary probabilities of states for the related Kripke structure constructed for the traffic system. There, the symmetry-based reduction of the state space allows to partially reduce the computational limitations of the numerical method.

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A reference implementation of the adaptive resolution scheme in ESPResSo

Computer Physics Communications ◽

10.1016/j.cpc.2010.04.013 ◽

2010 ◽

Vol 181 (8) ◽

pp. 1449-1454 ◽

Cited By ~ 18

Author(s):

Christoph Junghans ◽

Simón Poblete

Keyword(s):

Adaptive Resolution ◽

Resolution Scheme ◽

Reference Implementation

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A force field for virtual atom molecular mechanics of proteins

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0907674106 ◽

2009 ◽

Vol 106 (37) ◽

pp. 15667-15672 ◽

Cited By ~ 43

Author(s):

Anil Korkut ◽

Wayne A. Hendrickson

Keyword(s):

Force Field ◽

Molecular Mechanics ◽

Normal Mode ◽

Conformational Changes ◽

Normal Mode Analysis ◽

Coarse Grained ◽

Mode Analysis ◽

Biological Macromolecules ◽

Molecular Mechanics Calculations ◽

Low Degrees

Activities of many biological macromolecules involve large conformational transitions for which crystallography can specify atomic details of alternative end states, but the course of transitions is often beyond the reach of computations based on full-atomic potential functions. We have developed a coarse-grained force field for molecular mechanics calculations based on the virtual interactions of Cα atoms in protein molecules. This force field is parameterized based on the statistical distribution of the energy terms extracted from crystallographic data, and it is formulated to capture features dependent on secondary structure and on residue-specific contact information. The resulting force field is applied to energy minimization and normal mode analysis of several proteins. We find robust convergence in minimizations to low energies and energy gradients with low degrees of structural distortion, and atomic fluctuations calculated from the normal mode analyses correlate well with the experimental B-factors obtained from high-resolution crystal structures. These findings suggest that the virtual atom force field is a suitable tool for various molecular mechanics applications on large macromolecular systems undergoing large conformational changes.

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Hybrid MM/CG Webserver: Automatic Set Up of Molecular Mechanics/Coarse-Grained Simulations for Human G Protein-Coupled Receptor/Ligand Complexes

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2020.576689 ◽

2020 ◽

Vol 7 ◽

Cited By ~ 2

Author(s):

Jakob Schneider ◽

Rui Ribeiro ◽

Mercedes Alfonso-Prieto ◽

Paolo Carloni ◽

Alejandro Giorgetti

Keyword(s):

Molecular Mechanics ◽

G Protein ◽

Coarse Grained ◽

G Protein Coupled Receptor ◽

Receptor Ligand ◽

Coarse Grained Simulations ◽

Set Up ◽

G Protein Coupled

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Computation of conformational transitions in proteins by virtual atom molecular mechanics as validated in application to adenylate kinase

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0907684106 ◽

2009 ◽

Vol 106 (37) ◽

pp. 15673-15678 ◽

Cited By ~ 19

Author(s):

Anil Korkut ◽

Wayne A. Hendrickson

Keyword(s):

Molecular Mechanics ◽

Conformational Changes ◽

Adenylate Kinase ◽

Normal Modes ◽

Conformational Transitions ◽

The Other ◽

Coarse Grained ◽

Knowledge Based ◽

Comprehensive Knowledge ◽

Transition Pathways

Many proteins function through conformational transitions between structurally disparate states, and there is a need to explore transition pathways between experimentally accessible states by computation. The sizes of systems of interest and the scale of conformational changes are often beyond the scope of full atomic models, but appropriate coarse-grained approaches can capture significant features. We have designed a comprehensive knowledge-based potential function based on a Cα representation for proteins that we call the virtual atom molecular mechanics (VAMM) force field. Here, we describe an algorithm for using the VAMM potential to describe conformational transitions, and we validate this algorithm in application to a transition between open and closed states of adenylate kinase (ADK). The VAMM algorithm computes normal modes for each state and iteratively moves each structure toward the other through a series of intermediates. The move from each side at each step is taken along that normal mode showing greatest engagement with the other state. The process continues to convergence of terminal intermediates to within a defined limit—here, a root-mean-square deviation of 1 Å. Validations show that the VAMM algorithm is highly effective, and the transition pathways examined for ADK are compatible with other structural and biophysical information. We expect that the VAMM algorithm can address many biological systems.

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