Question

4. (8 points) You are interested in running molecular dynamics simulations of a protein of interest. You went to the protein databank and found some structures of your protein and analyzed their geometry by making a Ramachandran plot. Below are two plots corresponding to two separate structures. 1. Al seks WALA A COA 110 PEDAA4SER ate PALL AR L 01284 GLU HOS 153 GLU 41 .. 1851946 DA POLYS 103 ASN A 194 CY OB 297ASPO B 133 AKO GATALO MAMA 3ALA YA -1801 -1806 180 Phi 150 Phi là. a. Describe (in a couple sentences) what may be a cause of the differences in A and B. Overall how do these plots differentiate structure A and B? b. Which would you choose for your simulation? Explain.

Answer 1

Answer: To check the accuracy of the modelled 3D structures, a structure assessment is done on the basis on ϕ, ψ angle rearrangement based on Ramachandran plot analysis. The Ramachandran diagram plots ϕ to ψ conformational angles backbone for every residue in the protein. ϕ, ψ plots for individual proteins have been found to be the central for structure validation as ϕ, ψ values are not rearranged by the process of refinement and, that is why provides a sensitive indications about the local problem areas. These ϕ, ψ criteria have been accepted as a trustable protein structure validation aspect. There are 3 major components of validation of structure geometrically named as backbone conformation basically ϕ, ψ angles, Cα geometry and sidechain conformation, which signals the compatibility of backbone-sidechain.

Protein residues are placed on allowed, favored and the not allowed regions. The high-quality models have more than 90% of their residues which are expected to be found in the most favored regions of Ramachandran plot as shown in the figure below.

Ganoral Glycino - - -- - - - - -- 78 THB Wo Pre-Pro Proline 180 Wo *1 PRO -100 -180 180 -180 General Favoured Glycine Favoured Pre-Pro Favoured Proline Favoured General Allowed Glycine Allowed Pre-Pro Allowed Proline Allowed

a) In figure A maximum residues can be seen in favoured regions whereas in figure B many residues are in non-allowed regions. This occurs due to the distribution of the residues in the allowed and favoured regions.

b) Figure A follows a Ramachandran plot rule that proves it to be a more stable structure than that of in Figure B that is why we will choose Figure A containing protein structure for simulation.