title: The Parasol Protocol for computational mutagenesis.
abstract: To aid in the discovery and development of peptides and proteins as therapeutic agents, a virtual screen can be used to predict trends and direct workflow. We have developed the Parasol Protocol, a dynamic method implemented using the AMBER MD package, for computational site-directed mutagenesis. This tool can mutate between any pair of amino acids in a computationally expedient, automated manner. To demonstrate the potential of this methodology, we have employed the protocol to investigate a test case involving stapled peptides, and have demonstrated good agreement with experiment.
authors.affiliation: Department of Chemistry and Institute of Chemical Biology, Imperial College London, South Kensington Campus, Exhibition Road, London SW7 2AZ, UK.
authors.forename: P G A
authors.initials: PG
authors.lastname: Aronica
authors.affiliation: Bioinformatics Institute (A*STAR), 30 Biopolis Street, #07-01 Matrix, Singapore 138671 School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543.
authors.forename: C
authors.initials: C
authors.lastname: Verma
authors.affiliation: Department of Antibody Discovery and Protein Engineering, MedImmune, Aaron Klug Building, Granta Park, Cambridge CB21 6GH, UK.
authors.forename: B
authors.initials: B
authors.lastname: Popovic
authors.affiliation: Department of Chemistry and Institute of Chemical Biology, Imperial College London, South Kensington Campus, Exhibition Road, London SW7 2AZ, UK Liverpool John Moores University, 2 Rodney Street, Liverpool L1 2UA, UK r.leatherbarrow@imperial.ac.uk i.gould@imperial.ac.uk.
authors.forename: R J
authors.initials: RJ
authors.lastname: Leatherbarrow
authors.affiliation: Department of Chemistry and Institute of Chemical Biology, Imperial College London, South Kensington Campus, Exhibition Road, London SW7 2AZ, UK r.leatherbarrow@imperial.ac.uk i.gould@imperial.ac.uk.
authors.forename: I R
authors.initials: IR
authors.lastname: Gould
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003198:Computer Simulation; D006801:Humans; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010455:Peptides / Q000737:chemistry / Q000235:genetics; D011506:Proteins / Q000737:chemistry* / Q000235:genetics*; D012984:Software; D057188:Workflow
chemical_list: D010455:Peptides; D011506:Proteins
keywords: in silico mutation; molecular dynamics