title: In-Silico Template Selection of In-Vitro Evolved Kalata B1 of Oldenlandia Affinis for Scaffolding Peptide-Based Drug Design.
abstract: Structural stability of Oldenlandia affinis cyclotide, kalata B1 of native (1NB1) and two mutants 2F2I ([P20D, V21K] kB1) and 2F2J ([W19K, P20N, V21K] kB1) was investigated. Single model analysis showed high number of intra-molecular interactions followed by more proportion of beta sheet contents in [P20D, V21K] kB1 as compared to that of native and the other mutant of kalata B1. Further, the modern conformational sampling approach, an alternate to classical molecular dynamics was introduced, which revealed that the [P20D, V21K] kB1 was identified as structurally stable one, substantiated by various structural events viz., root mean square deviation, root mean square fluctuation, and angular deviation by Ramachandran plot. Moreover, the statistically validated contours of polar surface area, hydrogen bond distribution and the distance of disulfide bridges also supported the priority of [P20D, V21K] kB1 with respect to stability. From this work, it is proposed that the [P20D, V21K] kB1 (2F2I) could be the best template for scaffolding peptide based drug design.
authors.affiliation: Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology University, Vellore, 632014, Tamil Nadu, India.
authors.forename: B
authors.initials: B
authors.lastname: Senthilkumar
authors.affiliation: Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology University, Vellore, 632014, Tamil Nadu, India.
authors.forename: Prakash
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology University, Vellore, 632014, Tamil Nadu, India.
authors.forename: R
authors.initials: R
authors.lastname: Rajasekaran
mesh_terms: D047169:Cyclotides / Q000737:chemistry*; D015195:Drug Design; D056004:Molecular Dynamics Simulation; D032067:Oldenlandia / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*
chemical_list: D047169:Cyclotides; D010455:Peptides; C091930:kalata B1
keywords: CONFORMATIONAL SAMPLING; CYCLOTIDES; KALATA B1; OLDENLANDIA AFFINIS; STABILITY