A balance of van der Waals, electrostatic, and hydrophobic forces drive the folding and packing of protein side chains. Although such interactions between residues are often approximated as being pairwise additive, in reality, higher-order many-body contributions that depend on environment drive hydrophobic collapse and cooperative electrostatics. Beginning from dead-end elimination, we derive the first algorithm, to our knowledge, capable of deterministic global repacking of side chains compatible with many-body energy functions. The approach is applied to seven PCNA x-ray crystallographic data sets with resolutions 2.5-3.8 Å (mean 3.0 Å) using an open-source software. While PDB_REDO models average an Rfree value of 29.5% and MOLPROBITY score of 2.71 Å (77th percentile), dead-end elimination with the polarizable AMOEBA force field lowered Rfree by 2.8-26.7% and improved mean MOLPROBITY score to atomic resolution at 1.25 Å (100th percentile). For structural biology applications that depend on side-chain repacking, including x-ray refinement, homology modeling, and protein design, the accuracy limitations of pairwise additivity can now be eliminated via polarizable or quantum mechanical potentials.

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We also propose a website to host such a DBMS that can facilitate researchers to upload their data and perform analysis efficiently. Users can analyze their data using efficient functions implemented to access the data. Index structures are generated to store all results of analysis that may be interesting to other users, so that the results of analysis are readily available without the need to duplicate the analysis. The data upload feature can be made available through application program interfaces (APIs). Users can upload their data using the APIs. The DBMS takes care of generating indexes, storing results of analysis and retrieving efficiently, whenever users run analysis query or request information.

International audienc

No abstract