Gideon Lapidoth1, Jake Parker2,3, Jaime Prilusky4, Sarel J Fleishman1. 1. Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel. 2. Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Australia. 3. CSIRO Synthetic Biology Future Science Platform, Weizmann Institute of Science, Rehovot, Israel. 4. Bioinformatics & Biological Computing Unit, Weizmann Institute of Science, Rehovot, Israel.
Abstract
SUMMARY: Methods for antibody structure prediction rely on sequence homology to experimentally determined structures. Resulting models may be accurate but are often stereochemically strained, limiting their usefulness in modeling and design workflows. We present the AbPredict 2 web-server, which instead of using sequence homology, conducts a Monte Carlo-based search for low-energy combinations of backbone conformations to yield accurate and unstrained antibody structures. AVAILABILITY AND IMPLEMENTATION: We introduce several important improvements over the previous AbPredict implementation: (i) backbones and sidechains are now modeled using ideal bond lengths and angles, substantially reducing stereochemical strain, (ii) sampling of the rigid-body orientation at the light-heavy chain interface is improved, increasing model accuracy and (iii) runtime is reduced 20-fold without compromising accuracy, enabling the implementation of AbPredict 2 as a fully automated web-server (http://abpredict.weizmann.ac.il). Accurate and unstrained antibody model structures may in some cases obviate the need for experimental structures in antibody optimization workflows.
SUMMARY: Methods for antibody structure prediction rely on sequence homology to experimentally determined structures. Resulting models may be accurate but are often stereochemically strained, limiting their usefulness in modeling and design workflows. We present the AbPredict 2 web-server, which instead of using sequence homology, conducts a Monte Carlo-based search for low-energy combinations of backbone conformations to yield accurate and unstrained antibody structures. AVAILABILITY AND IMPLEMENTATION: We introduce several important improvements over the previous AbPredict implementation: (i) backbones and sidechains are now modeled using ideal bond lengths and angles, substantially reducing stereochemical strain, (ii) sampling of the rigid-body orientation at the light-heavy chain interface is improved, increasing model accuracy and (iii) runtime is reduced 20-fold without compromising accuracy, enabling the implementation of AbPredict 2 as a fully automated web-server (http://abpredict.weizmann.ac.il). Accurate and unstrained antibody model structures may in some cases obviate the need for experimental structures in antibody optimization workflows.
Authors: Vincent B Chen; W Bryan Arendall; Jeffrey J Headd; Daniel A Keedy; Robert M Immormino; Gary J Kapral; Laura W Murray; Jane S Richardson; David C Richardson Journal: Acta Crystallogr D Biol Crystallogr Date: 2009-12-21
Authors: Rahmad Akbar; Habib Bashour; Puneet Rawat; Philippe A Robert; Eva Smorodina; Tudor-Stefan Cotet; Karine Flem-Karlsen; Robert Frank; Brij Bhushan Mehta; Mai Ha Vu; Talip Zengin; Jose Gutierrez-Marcos; Fridtjof Lund-Johansen; Jan Terje Andersen; Victor Greiff Journal: MAbs Date: 2022 Jan-Dec Impact factor: 5.857
Authors: Julia Koehler Leman; Brian D Weitzner; Steven M Lewis; Jared Adolf-Bryfogle; Nawsad Alam; Rebecca F Alford; Melanie Aprahamian; David Baker; Kyle A Barlow; Patrick Barth; Benjamin Basanta; Brian J Bender; Kristin Blacklock; Jaume Bonet; Scott E Boyken; Phil Bradley; Chris Bystroff; Patrick Conway; Seth Cooper; Bruno E Correia; Brian Coventry; Rhiju Das; René M De Jong; Frank DiMaio; Lorna Dsilva; Roland Dunbrack; Alexander S Ford; Brandon Frenz; Darwin Y Fu; Caleb Geniesse; Lukasz Goldschmidt; Ragul Gowthaman; Jeffrey J Gray; Dominik Gront; Sharon Guffy; Scott Horowitz; Po-Ssu Huang; Thomas Huber; Tim M Jacobs; Jeliazko R Jeliazkov; David K Johnson; Kalli Kappel; John Karanicolas; Hamed Khakzad; Karen R Khar; Sagar D Khare; Firas Khatib; Alisa Khramushin; Indigo C King; Robert Kleffner; Brian Koepnick; Tanja Kortemme; Georg Kuenze; Brian Kuhlman; Daisuke Kuroda; Jason W Labonte; Jason K Lai; Gideon Lapidoth; Andrew Leaver-Fay; Steffen Lindert; Thomas Linsky; Nir London; Joseph H Lubin; Sergey Lyskov; Jack Maguire; Lars Malmström; Enrique Marcos; Orly Marcu; Nicholas A Marze; Jens Meiler; Rocco Moretti; Vikram Khipple Mulligan; Santrupti Nerli; Christoffer Norn; Shane Ó'Conchúir; Noah Ollikainen; Sergey Ovchinnikov; Michael S Pacella; Xingjie Pan; Hahnbeom Park; Ryan E Pavlovicz; Manasi Pethe; Brian G Pierce; Kala Bharath Pilla; Barak Raveh; P Douglas Renfrew; Shourya S Roy Burman; Aliza Rubenstein; Marion F Sauer; Andreas Scheck; William Schief; Ora Schueler-Furman; Yuval Sedan; Alexander M Sevy; Nikolaos G Sgourakis; Lei Shi; Justin B Siegel; Daniel-Adriano Silva; Shannon Smith; Yifan Song; Amelie Stein; Maria Szegedy; Frank D Teets; Summer B Thyme; Ray Yu-Ruei Wang; Andrew Watkins; Lior Zimmerman; Richard Bonneau Journal: Nat Methods Date: 2020-06-01 Impact factor: 28.547
Authors: Richard A Norman; Francesco Ambrosetti; Alexandre M J J Bonvin; Lucy J Colwell; Sebastian Kelm; Sandeep Kumar; Konrad Krawczyk Journal: Brief Bioinform Date: 2020-09-25 Impact factor: 11.622