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A Conformational Analysis Study on the Melanocortin 4 Receptor Using Multiple Molecular Dynamics Simulations
Author(s) -
Shahlaei Mohsen,
Mousavi Atefeh
Publication year - 2015
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12495
Subject(s) - molecular dynamics , context (archaeology) , biological system , homology modeling , biomolecule , principal component analysis , representation (politics) , computer science , conformational ensembles , chemistry , computational biology , computational chemistry , artificial intelligence , biology , biochemistry , paleontology , politics , political science , law , enzyme
Taking into account the uncertainties involved in 3D model of biomolecule developed by homology modeling ( HM ), it is important to opportunely validate the initial structure before employing for different purposes such as drug design. Extended simulation times and the necessity of correct representation of interactions within the protein and the nearby molecules impose significant limitations on molecular dynamics ( MD )‐based refinement of structures developed by HM . Consequently, there is a pressing requirement for more efficient methods for HM and subsequent validation of developed structure. Multiple MD simulation runs are well suited for producing ensembles of structures. In this context, a computational investigation was presented to study the structure of melanocortin 4 receptor (MC4R) using molecular dynamics ( MD ) simulations in explicit phospholipids bilayer. Several MD runs with different initial velocities were employed to sample conformations in the neighborhood of the native structure of receptor, collecting trajectories spanning 0.21 ms. The coherence between the results, different structural analysis, and the convergence of parameters derived by principal component analysis ( PCA ) shows that an accurate description of the MC4R conformational space around the native state was achieved by multiple MD trajectories.