TY - JOUR

T1 - MORPH-PRO

T2 - A novel algorithm and web server for protein morphing

AU - Castellana, Natalie E.

AU - Lushnikov, Andrey

AU - Rotkiewicz, Piotr

AU - Sefcovic, Natasha

AU - Pevzner, Pavel A.

AU - Godzik, Adam

AU - Vyatkina, Kira

N1 - Funding Information: We would like to acknowledge the valuable input provided by Mallika Veeramalai, Piotr Cieplak, and Lukasz Jaroszewski (Joint Center for Structural Genomics). We thank Hongbin Yuan and Maurizio Pellechia at the Sanford-Burnham Medical Research Institute for input on protein docking. We also thank all the members of the Joint Center for Molecular Modeling for helpful discussions. The Joint Center for Molecular Modeling is funded by the National Institute of General Medical Sciences [P20 GM07622] and is a part of the Protein Structure Initiative. NEC was supported in part by the NSF IGERT training grant [DGE-0504645]. PAP, AL and KV were supported by the Government of the Russian Federation (grant 11.G34.31.0018).

PY - 2013/7/11

Y1 - 2013/7/11

N2 - Background: Proteins are known to be dynamic in nature, changing from one conformation to another while performing vital cellular tasks. It is important to understand these movements in order to better understand protein function. At the same time, experimental techniques provide us with only single snapshots of the whole ensemble of available conformations. Computational protein morphing provides a visualization of a protein structure transitioning from one conformation to another by producing a series of intermediate conformations.Results: We present a novel, efficient morphing algorithm, Morph-Pro based on linear interpolation. We also show that apart from visualization, morphing can be used to provide plausible intermediate structures. We test this by using the intermediate structures of a c-Jun N-terminal kinase (JNK1) conformational change in a virtual docking experiment. The structures are shown to dock with higher score to known JNK1-binding ligands than structures solved using X-Ray crystallography. This experiment demonstrates the potential applications of the intermediate structures in modeling or virtual screening efforts.Conclusions: Visualization of protein conformational changes is important for characterization of protein function. Furthermore, the intermediate structures produced by our algorithm are good approximations to true structures. We believe there is great potential for these computationally predicted structures in protein-ligand docking experiments and virtual screening. The Morph-Pro web server can be accessed at http://morph-pro.bioinf.spbau.ru.

AB - Background: Proteins are known to be dynamic in nature, changing from one conformation to another while performing vital cellular tasks. It is important to understand these movements in order to better understand protein function. At the same time, experimental techniques provide us with only single snapshots of the whole ensemble of available conformations. Computational protein morphing provides a visualization of a protein structure transitioning from one conformation to another by producing a series of intermediate conformations.Results: We present a novel, efficient morphing algorithm, Morph-Pro based on linear interpolation. We also show that apart from visualization, morphing can be used to provide plausible intermediate structures. We test this by using the intermediate structures of a c-Jun N-terminal kinase (JNK1) conformational change in a virtual docking experiment. The structures are shown to dock with higher score to known JNK1-binding ligands than structures solved using X-Ray crystallography. This experiment demonstrates the potential applications of the intermediate structures in modeling or virtual screening efforts.Conclusions: Visualization of protein conformational changes is important for characterization of protein function. Furthermore, the intermediate structures produced by our algorithm are good approximations to true structures. We believe there is great potential for these computationally predicted structures in protein-ligand docking experiments and virtual screening. The Morph-Pro web server can be accessed at http://morph-pro.bioinf.spbau.ru.

KW - Molecular docking

KW - Protein morphing

KW - Virtual screening

UR - http://www.scopus.com/inward/record.url?scp=84880001367&partnerID=8YFLogxK

U2 - 10.1186/1748-7188-8-19

DO - 10.1186/1748-7188-8-19

M3 - Article

AN - SCOPUS:84880001367

VL - 8

JO - Algorithms for Molecular Biology

JF - Algorithms for Molecular Biology

SN - 1748-7188

IS - 1

M1 - 19

ER -