title: A Quantitative Measure of Conformational Changes in Apo, Holo and Ligand-Bound Forms of Enzymes.
abstract: Determination of the native geometry of the enzymes and ligand complexes is a key step in the process of structure-based drug designing. Enzymes and ligands show flexibility in structural behavior as they come in contact with each other. When ligand binds with active site of the enzyme, in the presence of cofactor some structural changes are expected to occur in the active site. Motivation behind this study is to determine the nature of conformational changes as well as regions where such changes are more pronounced. To measure the structural changes due to cofactor and ligand complex, enzyme in apo, holo and ligand-bound forms is selected. Enzyme data set was retrieved from protein data bank. Fifteen triplet groups were selected for the analysis of structural changes based on selection criteria. Structural features for selected enzymes were compared at the global as well as local region. Accessible surface area for the enzymes in entire triplet set was calculated, which describes the change in accessible surface area upon binding of cofactor and ligand with the enzyme. It was observed that some structural changes take place during binding of ligand in the presence of cofactor. This study will helps in understanding the level of flexibility in protein-ligand interaction for computer-aided drug designing.
authors.affiliation: Department of Computational Biology and Bioinformatics, JSBB, SHIATS, Allahabad, 211007, India.
authors.forename: Satendra
authors.initials: S
authors.lastname: Singh
authors.affiliation: Centre for Research in Nanotechnology and Science, Indian Institute of Technology, Mumbai, 400076, India.
authors.forename: Atul Kumar
authors.initials: AK
authors.lastname: Singh
authors.affiliation: Apex Bioinformatics Centre, Department of Biotechnology, Ministry of Science and Technology, CGO Complex, Lodhi Road, New Delhi, 110003, India.
authors.forename: Gulshan
authors.initials: G
authors.lastname: Wadhwa
authors.affiliation: Department of Biotechnology, Institute of Biosciences and Biotechnology, Chhatrapati Shahu Ji Maharaj University, Kanpur, Uttar Pradesh, 208024, India. answer.dev@gmail.com.
authors.forename: Dev Bukhsh
authors.initials: DB
authors.lastname: Singh
authors.affiliation: School of Biotechnology, Gautam Buddha University, Greater Noida, Uttar Pradesh, 201308, India.
authors.forename: Seema
authors.initials: S
authors.lastname: Dwivedi
authors.affiliation: Department of Computational Biology and Bioinformatics, JSBB, SHIATS, Allahabad, 211007, India.
authors.forename: Budhayash
authors.initials: B
authors.lastname: Gautam
authors.affiliation: Department of Biological Sciences, SHIATS, Allahabad, 211007, India.
authors.forename: Pramod W
authors.initials: PW
authors.lastname: Ramteke
mesh_terms: D018360:Crystallography, X-Ray; D030562:Databases, Protein; D004798:Enzymes / Q000737:chemistry*; D008024:Ligands; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D004798:Enzymes; D008024:Ligands
keywords: Active site; Cofactor; Enzymes; Flexibility; Structural changes