Exploring the Electronic Structure of Knotted Proteins using Semiempirical Calculations and Quantum Chemical Descriptors

Geometrical knots are rare structural arrangements in proteins in which the polypeptide chain ties itself into a knot, which is very intriguing due to the uncertainty of their impact on the protein properties. Presently, classical molecular dynamics is the most employed technique in the few studies found on this topic, which means that any information on how the presence of knots affects the reactivity and electronic properties of proteins is even scarcer. Thus, using the new software, PRIMoRDiA, developed by our group to explore the electronic structure of biological macromolecules, we evaluated several local quantum chemical descriptors to unveil relevant patterns potentially originating from the presence of the geometrical knot in two proteins, as a case of study. We compared several sampled structures from two enzymes that are highly similar in both tertiary structure and function, but one of them has a knot whereas the other does not. We found that the same amino-acid residues in the knot core have statistically larger values for the unknotted protein, for both hard-hard and soft-soft interaction descriptors. Additionally, we explored the variation in several reactivity and other quantum chemical properties calculated from a set of snapshot structures of whole proteins. We present a computationally feasible protocol that combines structures sampled from nanoscale molecular dynamics trajectories, semiempirical calculations of the entire protein atom set and the use of our software PRIMoRDiA to compute molecular quantum chemical descriptors. From this protocol we showed that the is possible to separate the contribution of the geometrical knot to the reactivity and other electronic structure properties.

This zip file contains:

Structural/rep.c0_3kzn_310_hardness_A.pdb    PDB with Hardness type A descriptor calculated by PRIMoRDIA for the structural reactivity analysis of the non-knotted protein at 310K. Frame selected from the first cluster of clusterized moleculer dynamics. 
Structural/rep.c0_3kzn_310_hardness_B.pdb    PDB with Hardness type B descriptor calculated by PRIMoRDIA for the structural reactivity analysis of the non-knotted protein at 310K. Frame selected from the first cluster of clusterized moleculer dynamics. 
Structural/rep.c0_3kzn_310_RAS.pdb    PDB with Radical Susceptibility Attack descriptor calculated by PRIMoRDIA for the structural reactivity analysis of the non-knotted protein at 310K. Frame selected from the first cluster of clusterized moleculer dynamics. 
Structural/rep.c0_3kzn_310_softness.pdb    PDB with local softness descriptor calculated by PRIMoRDIA for the structural reactivity analysis of the non-knotted protein at 310K. Frame selected from the first cluster of clusterized moleculer dynamics. 
Structural/rep.c0_4jqo_310K_hardness_A.pdb    PDB with Hardness type A descriptor calculated by PRIMoRDIA for the structural reactivity analysis of the knotted protein at 310K. Frame selected from the first cluster of clusterized moleculer dynamics. 
Structural/rep.c0_4jqo_310K_hardness_B.pdb    PDB with Hardness type B descriptor calculated by PRIMoRDIA for the structural reactivity analysis of the knotted protein at 310K. Frame selected from the first cluster of clusterized moleculer dynamics. 
Structural/rep.c0_4jqo_310K_hardness_C.pdb    PDB with Hardness type C descriptor calculated by PRIMoRDIA for the structural reactivity analysis of the knotted protein at 310K. Frame selected from the first cluster of clusterized moleculer dynamics. 
Structural/rep.c0_4jqo_310K_RAS.pdb        PDB with Radical Susceptibility Attack descriptor calculated by PRIMoRDIA for the structural reactivity analysis of the knotted protein at 310K. Frame selected from the first cluster of clusterized moleculer dynamics. 
Structural/rep.c0_4jqo_310K_softness.pdb    PDB with local softness descriptor calculated by PRIMoRDIA for the structural reactivity analysis of the knotted protein at 310K. Frame selected from the first cluster of clusterized moleculer dynamics. 
Statistical/3kzn_310_data_stat            Statistics of all the descriptors for the knotted protein at 310K.
Statistical/3kzn_310residues_data_frames    Values of the descriptors condensed by the residues for each frames for the knotted protein at 310K.
Statistical/3kzn_310residues_data_stat        Statistics of the descriptors condensed by selected residues in the knot region for each frames for the knotted protein at 310K.
Statistical/3kzn_373protein_data_stat        Statistics of the descriptors condensed by selected residues in the knot region for each frames for the knotted protein at 373K.
Statistical/3kzn_373residues_data_frames    Values of the descriptors condensed by the residues for each frames for the knotted protein at 373K.
Statistical/3kzn_373residues_data_stat        Statistics of all the descriptors for the knotted protein at 373K.
Statistical/4jqo_373residues_data_stat        Statistics of all the descriptors for the non-knotted protein at 373K.
Statistical/4jqo_373residues_data_frames    Values of the descriptors condensed by the residues for each frames for the non-knotted protein at 373K.
Statistical/4jqo_373protein_data_stat        Statistics of the descriptors condensed by selected residues in the non-knotted region for each frames for the knotted protein at 373K.
Statistical/4jqo_310protein_data_stat        Statistics of all the descriptors for the non-knotted protein at 310K.
Statistical/4jqo_310residues_data_frames    Values of the descriptors condensed by the residues for each frames for the non-knotted protein at 310K.
Statistical/4jqo_310residues_data_stat        Statistics of all the descriptors for the knotted protein at 310K.
Statistical/analysis_pt.R            Script in R to do the analysis on the paper 
Statistical/rd_data_pt                Data for PCA and other statistical analysis.