title: Conformational changes and allosteric communications in human serum albumin due to ligand binding.
abstract: It is well recognized that knowledge of structure alone is not sufficient to understand the fundamental mechanism of biomolecular recognition. Information of dynamics is necessary to describe motions involving relevant conformational states of functional importance. We carried out principal component analysis (PCA) of structural ensemble, derived from 84 crystal structures of human serum albumin (HSA) with different ligands and/or different conditions, to identify the functionally important collective motions, and compared with the motions along the low-frequency modes obtained from normal mode analysis of the elastic network model (ENM) of unliganded HSA. Significant overlap is observed in the collective motions derived from PCA and ENM. PCA and ENM analysis revealed that ligand selects the most favored conformation from accessible equilibrium structures of unliganded HSA. Further, we analyzed dynamic network obtained from molecular dynamics simulations of unliganded HSA and fatty acids- bound HSA. Our results show that fatty acids-bound HSA has more robust community network with several routes to communicate among different parts of the protein. Critical nodes (residues) identified from dynamic network analysis are in good agreement with allosteric residues obtained from sequence-based statistical coupling analysis method. This work underscores the importance of intrinsic structural dynamics of proteins in ligand recognition and can be utilized for the development of novel drugs with optimum activity.
authors.affiliation: a Department of Chemistry , Indian Institute of Science Education and Research Bhopal , Bhauri, Bhopal , Madhya Pradesh 462066 , India.
authors.forename: Navjeet
authors.initials: N
authors.lastname: Ahalawat
authors.forename: Rajesh K
authors.initials: RK
authors.lastname: Murarka
mesh_terms: D000495:Allosteric Site; D018360:Crystallography, X-Ray; D005227:Fatty Acids / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D056004:Molecular Dynamics Simulation; D009038:Motion; D011485:Protein Binding; D011487:Protein Conformation; D012709:Serum Albumin / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D005227:Fatty Acids; D008024:Ligands; D012709:Serum Albumin
keywords: X-ray ensemble; allostery; dynamic network analysis; elastic network model; human serum albumin; principal component analysis; statistical coupling analysis