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[…] um of the van der Waals contribution of all atoms; EsolvH and EsolvP count for the solvation energy for apolar and polar groups, respectively; Ewb is the water bridge hydrogen bonding between water and protein; Ehb is the intra-molecule hydrogen-bonding; Eel counts for the electrostatic contribution of interactions between charged groups; Emc and Esc are entropy costs for fixing main-chain and side-chain atoms in a particular conformation, respectively; and Eclash counts for the penalty from atomic steric overlaps. The parameters f1–9 were trained by maximizing the correlation between the calculated and experimental free-energy changes on a set of experimental residue mutants. The detail of FoldX potential design and parameterization can be found in Refs , . We used the default parameters for the FoldX calculation, except for the van der Waal weight f1 which was increased to 0.33 to eliminate the extra steric clashes observed in our simulations. Since FoldX potential is full-atomic, we use SCWRL V4.0 to construct the side-chain conformations after each MC movement., To balance the two parts energy terms which are derived from different resources, we renormalized the energy terms based on their deviations:(3)where and δE are average and standard deviation of the energy scores calculated from previous steps of simulations., The weight parameters in and (w1–5) were determined on a set of 625 non-redundant training proteins that are non-homologous to the test set and case study proteins (see For w1–3 in , the weights are decided by the relative accuracy of the individual feature predictions, i.e. w1 = C*ASS, w2 = C*ASA, w3 = C*ATA, where ASS, ASA and ATA are the number of correctly predicted residues on secondary structure (SS), solvent accessibility (SA) and torsion angles (TA), respectively, divided by the total number of residues on the training proteins. C is the parameter to balance the average magnitude of feature predictions with that of the profile term. The final weights for are: w1 = 1.58, w2 = 2.45, w3 = 1. For , the weights were adjusted so that the average contribution from the evolution terms and the physics based terms are comparable based […]

Pipeline specifications

Software tools FoldX, SCWRL, EvoDesign
Organisms Mycobacterium tuberculosis
Diseases Communicable Diseases, Death, Gram-Positive Bacterial Infections