title: Pipeline for inferring protein function from dynamics using coarse-grained molecular mechanics forcefield.
abstract: Dynamics is integral to the function of proteins, yet the use of molecular dynamics (MD) simulation as a technique remains under-explored for molecular function inference. This is more important in the context of genomics projects where novel proteins are determined with limited evolutionary information. Recently we developed a method to match the query protein's flexible segments to infer function using a novel approach combining analysis of residue fluctuation-graphs and auto-correlation vectors derived from coarse-grained (CG) MD trajectory. The method was validated on a diverse dataset with sequence identity between proteins as low as 3%, with high function-recall rates. Here we share its implementation as a publicly accessible web service, named DynFunc (Dynamics Match for Function) to query protein function from ≥1 µs long CG dynamics trajectory information of protein subunits. Users are provided with the custom-developed coarse-grained molecular mechanics (CGMM) forcefield to generate the MD trajectories for their protein of interest. On upload of trajectory information, the DynFunc web server identifies specific flexible regions of the protein linked to putative molecular function. Our unique application does not use evolutionary information to infer molecular function from MD information and can, therefore, work for all proteins, including moonlighting and the novel ones, whenever structural information is available. Our pipeline is expected to be of utility to all structural biologists working with novel proteins and interested in moonlighting functions.
authors.affiliation: Institute Mathematics Initiative, Indian Institute of Science, Bengaluru 560012, India.
authors.forename: Pratiti
authors.initials: P
authors.lastname: Bhadra
authors.affiliation: Institute Mathematics Initiative, Indian Institute of Science, Bengaluru 560012, India; Computational and Data Sciences, Indian Institute of Science, Bengaluru 560012, India. Electronic address: dpal@cds.iisc.ac.in.
authors.forename: Debnath
authors.initials: D
authors.lastname: Pal
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D003198:Computer Simulation; D008954:Models, Biological; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping / Q000379:methods*; D011506:Proteins / Q000737:chemistry* / Q000145:classification / Q000648:ultrastructure*; D020539:Sequence Analysis, Protein / Q000379:methods*; D013314:Stress, Mechanical; D013329:Structure-Activity Relationship
chemical_list: D011506:Proteins
keywords: Database; Dynamics; Forcefield; Molecular function; Simulation