Structural mining: self-consistent design on flexible protein-peptide docking and transferable binding affinity potential

Journal of the American Chemical Society
Zhijie LiuEugene I Shakhnovich

Abstract

A flexible protein-peptide docking method has been designed to consider not only ligand flexibility but also the flexibility of the protein. The method is based on a Monte Carlo annealing process. Simulations with a distance root-mean-square (dRMS) virtual energy function revealed that the flexibility of protein side chains was as important as ligand flexibility for successful protein-peptide docking. On the basis of mean field theory, a transferable potential was designed to evaluate distance-dependent protein-ligand interactions and atomic solvation energies. The potential parameters were developed using a self-consistent process based on only 10 known complex structures. The effectiveness of each intermediate potential was judged on the basis of a Z score, approximating the gap between the energy of the native complex and the average energy of a decoy set. The Z score was determined using experimentally determined native structures and decoys generated by docking with the intermediate potentials. Using 6600 generated decoys and the Z score optimization criterion proposed in this work, the developed potential yielded an acceptable correlation of R(2) = 0.77, with binding free energies determined for known MHC I complexes (Cla...Continue Reading

References

Jul 22, 1976·Nature·J A McCammonP G Wolynes
Jul 20, 1973·Science·C B Anfinsen
Aug 23, 1996·Journal of Molecular Biology·M RareyG Klebe
Aug 1, 1996·Journal of Computer-aided Molecular Design·G M MorrisA J Olson
Dec 20, 1996·Journal of Molecular Biology·L A Mirny, E I Shakhnovich
Apr 4, 1997·Journal of Molecular Biology·G JonesR Taylor
Oct 14, 1998·Journal of Molecular Biology·L A Mirny, E I Shakhnovich
Aug 24, 2000·Proceedings of the National Academy of Sciences of the United States of America·L A MirnyE I Shakhnovich
Apr 17, 2001·Journal of Molecular Biology·J ShimadaE I Shakhnovich
Jan 25, 2002·Proteins·Lin JiangLuhua Lai
Jun 14, 2002·Journal of Medicinal Chemistry·Alexey V Ishchenko, Eugene I Shakhnovich
May 23, 2003·Protein Science : a Publication of the Protein Society·Martin Zacharias
Sep 15, 1961·Proceedings of the National Academy of Sciences of the United States of America·C B ANFINSENF H WHITE

❮ Previous
Next ❯

Citations

Mar 12, 2013·Bioinformatics·Zhiqiang YanJin Wang
Jan 11, 2013·Open Biology·Atanas Patronov, Irini Doytchinova
Aug 31, 2011·PLoS Computational Biology·Iskra Staneva, Stefan Wallin
Nov 10, 2013·PLoS Computational Biology·Arnab Bhattacherjee, Stefan Wallin
Aug 25, 2012·Future Medicinal Chemistry·Joseph Audie, Jon Swanson
Feb 18, 2016·Journal of Computer-aided Molecular Design·Zhiqiang Yan, Jin Wang
Sep 8, 2009·Journal of Molecular Biology·Iskra Staneva, Stefan Wallin
Jun 30, 2007·Biophysical Chemistry·Joseph Audie, Suzanne Scarlata
May 23, 2012·Proteins·Vishwesh Venkatraman, David W Ritchie
Oct 5, 2013·IEEE/ACM Transactions on Computational Biology and Bioinformatics·Stefan IvanovIrini Doytchinova
Feb 21, 2006·Current Opinion in Structural Biology·Alexandre M J J Bonvin
Apr 11, 2017·PLoS Computational Biology·Lenna X PetersonDaisuke Kihara
Dec 26, 2018·Current Topics in Medicinal Chemistry·Dinler A AntunesLydia E Kavraki
Mar 14, 2018·Scientific Reports·Dinler A AntunesLydia E Kavraki
Dec 1, 2010·Biophysics Reviews·L RamyaNamasivayam Gautham
Apr 23, 2008·Journal of Chemical Information and Modeling·Hiroaki FukunishiJiro Shimada
Dec 13, 2018·Journal of Chemical Theory and Computation·Francesca NerattiniIvan Coluzza

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.