title: Overcoming potential energy distortions in constrained internal coordinate molecular dynamics simulations.
abstract: The Internal Coordinate Molecular Dynamics (ICMD) method is an attractive molecular dynamics (MD) method for studying the dynamics of bonded systems such as proteins and polymers. It offers a simple venue for coarsening the dynamics model of a system at multiple hierarchical levels. For example, large scale protein dynamics can be studied using torsional dynamics, where large domains or helical structures can be treated as rigid bodies and the loops connecting them as flexible torsions. ICMD with such a dynamic model of the protein, combined with enhanced conformational sampling method such as temperature replica exchange, allows the sampling of large scale domain motion involving high energy barrier transitions. Once these large scale conformational transitions are sampled, all-torsion, or even all-atom, MD simulations can be carried out for the low energy conformations sampled via coarse grained ICMD to calculate the energetics of distinct conformations. Such hierarchical MD simulations can be carried out with standard all-atom forcefields without the need for compromising on the accuracy of the forces. Using constraints to treat bond lengths and bond angles as rigid can, however, distort the potential energy landscape of the system and reduce the number of dihedral transitions as well as conformational sampling. We present here a two-part solution to overcome such distortions of the potential energy landscape with ICMD models. To alleviate the intrinsic distortion that stems from the reduced phase space in torsional MD, we use the Fixman compensating potential. To additionally alleviate the extrinsic distortion that arises from the coupling between the dihedral angles and bond angles within a force field, we propose a hybrid ICMD method that allows the selective relaxing of bond angles. This hybrid ICMD method bridges the gap between all-atom MD and torsional MD. We demonstrate with examples that these methods together offer a solution to eliminate the potential energy distortions encountered in constrained ICMD simulations of peptide molecules.
authors.affiliation: Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA.
authors.forename: Saugat
authors.initials: S
authors.lastname: Kandel
authors.affiliation: Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA.
authors.forename: Romelia
authors.initials: R
authors.lastname: Salomon-Ferrer
authors.affiliation: Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA.
authors.forename: Adrien B
authors.initials: AB
authors.lastname: Larsen
authors.affiliation: Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, Pasadena, California 91109, USA.
authors.forename: Abhinandan
authors.initials: A
authors.lastname: Jain
authors.affiliation: Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA.
authors.forename: Nagarajan
authors.initials: N
authors.lastname: Vaidehi
mesh_terms: D056004:Molecular Dynamics Simulation; D011108:Polymers / Q000737:chemistry; D011506:Proteins / Q000737:chemistry
chemical_list: D011108:Polymers; D011506:Proteins
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