Abstract
BackgroundElucidating the three-dimensional structure of a higher-order molecular assembly formed by interacting molecular units, a problem commonly known as docking, is central to unraveling the molecular basis of cellular activities. Though protein assemblies are ubiquitous in the cell, it is currently challenging to predict the native structure of a protein assembly in silico.MethodsThis work proposes HopDock, a novel search algorithm for protein-protein docking. HopDock efficiently obtains an ensemble of low-energy dimeric configurations, also known as decoys, that can be effectively used by ab-initio docking protocols. HopDock is based on the Basin Hopping (BH) framework which perturbs the structure of a dimeric configuration and then follows it up with an energy minimization to explicitly sample a local minimum of a chosen energy function. This process is repeated in order to sample consecutive energy minima in a trajectory-like fashion. HopDock employs both geometry and evolutionary conservation analysis to narrow down the interaction search space of interest for the purpose of efficiently obtaining a diverse decoy ensemble.Results and conclusionsA detailed analysis and a comparative study on seventeen different dimers shows HopDock obtains a broad view of the energy surface near the native dimeric structure and samples many near-native configurations. The results show that HopDock has high sampling capability and can be employed to effectively obtain a large and diverse ensemble of decoy configurations that can then be further refined in greater structural detail in ab-initio docking protocols.
Highlights
Elucidating the three-dimensional structure of a higher-order molecular assembly formed by interacting molecular units, a problem commonly known as docking, is central to unraveling the molecular basis of cellular activities
When the number of protein units is limited to two, the problem of predicting the biologically-active or native structure formed upon docking of the units onto each other is known as protein docking
The HopDock algorithm we propose in this paper can be considered to fall in this category, using a simple energy function to refine dimeric configurations found by essentially matching geometricallycomplementary regions
Summary
Elucidating the three-dimensional structure of a higher-order molecular assembly formed by interacting molecular units, a problem commonly known as docking, is central to unraveling the molecular basis of cellular activities. When the number of protein units is limited to two, the problem of predicting the biologically-active or native structure formed upon docking of the units onto each other is known as protein docking This problem is challenging to address in-silico for several reasons. If no a priori information is available, the problem requires searching over a space of N * M + 6 dimensions In this space, N and M parameters are needed to instantiate the two protein units in different tertiary structures, and 6 parameters are used to represent the rotation and translation components of the spatial arrangement of one unit onto the other, effectively docking the unit designated as moving onto the one designated as the base
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
