The third group of variants with located superimposition change up to 12?? for many structural regions included the following variants; 20A/S.L18F and B.1.429 (21C/452R at the Furin cleavage, which both hidden a Furin region. conformational change impact of D614G in allowing the polybasic Furin cleavage site (682RRARS686) to be closer to the receptor-binding domain (RBD) and hence more exposed to cleavage. The presence of D614G in any clade or subclade, such as 20A, B.1.1.7 (20I/501Y.V1) or Alpha, B.1.351 (20H/501Y.V2) or Beta, P.1 (20J/501Y.V3) or Gamma, B.1.617.2 (21A/478K.V1) or Delta, has increased its stability and flexibility and unified the superimposition among all clades which might impact the virus ability to escape the antibodies neutralization by changing the antigenicity drift Astragaloside II of the protein three-dimensional (3D) structure from the wild type clade 19A; this is in agreement with previous study. In conclusion, a new design for the current vaccines to include at least the mutation D614G is immediately needed. by DynaMut. thead th rowspan=”1″ colspan=”1″ # /th th rowspan=”1″ colspan=”1″ SARS-CoV-2 Spike br / Variants of interest /th th rowspan=”1″ colspan=”1″ Spike Protein Region /th th rowspan=”1″ colspan=”1″ G DynaMut em kcal/mol /em /th th rowspan=”1″ colspan=”1″ SVib ENCoM em kcal.mol /em em ?1 /em em .K /em em ?1 /em /th th rowspan=”1″ colspan=”1″ Global Percentage from GSAID br / August 8, 2021 /th th rowspan=”1″ colspan=”1″ Interatomic interaction with surrounding Amino Acids for increasing flexibility only (?) Lost interatomic interaction br / (+) Gained interatomic interaction /th /thead 1L5FSP?0.105 (Destabilizing)?0.258 (Decrease of molecule flexibility)3.492L18FNTD0.985 (Stabilizing)?0.641 (Decrease of molecule flexibility)5.943D80ANTD0.692 (Stabilizing)0.199 (Increase of molecule flexibility)1.19-W64,-F69,-Y26,-P82,-H66,+L2424S98FNTD0.788 (Stabilizing)?0.348 (Decrease of molecule flexibility)1.405A222VNTD2.134 (Stabilizing)?0.547 (Decrease of molecule flexibility)8.136A262SNTD0.828 (Stabilizing)?0.408 Decrease of molecule flexibility)0.547P272LNTD1.297 (Stabilizing)?0.467 (Decrease of molecule flexibility)0.388K417?NRBD?0.287 (Destabilizing)0.588 (Increase of molecule flexibility)1.299N439KRBD2.132 (Stabilizing)?0.703 (Decrease of molecule flexibility)1.2510L452RRBD0.227 (Stabilizing)?0.014 (Decrease of molecule flexibility)17.7311Y453FRBD?0.087 (Destabilizing)?0.131 (Decrease of molecule flexibility)0.0712S477?NRBD0.038 (Stabilizing)?0.002 (Decrease of molecule flexibility)2.5113E484KRBD?0.187 (Destabilizing)0.490 (Increase of molecule flexibility)6.14-Y489,-F490?+F48614E484QRBD?0.488 (Destabilizing)0.389 (Increase of molecule flexibility)0.28-Y489,-F49015N501TRBD0.701 (Stabilizing)?0.131 (Decrease of molecule flexibility)0.1516N501YRBD0.502 (Stabilizing)?0.211 (Decrease of molecule flexibility)43.9117E583DS1?0.365 (Destabilizing)0.215 (Increase of molecule flexibility)0.32-L533,K53518D614GPRE-FURIN0.292 (Stabilizing)0.103 (Increase of molecule flexibility)98.05-R64619Q675HPRE-FURIN?0.621 (Destabilizing)0.332 (Increase of molecule flexibility)0.79+S691,-Y66020Q675PPRE-FURIN?0.125 (Destabilizing)0.254 (Increase of molecule flexibility)0.00+S691,+S673,+Q677,+Q690,-Y66021Q677HPRE-FURIN2.661 (Stabilizing)?0.760 (Decrease of molecule flexibility)1.3722Q677PPRE-FURIN1.053 (Stabilizing)?0.176 (Decrease of molecule flexibility)0.1823P681HPRE-FURIN0.297 (Stabilizing)?0.035(Decrease of molecule flexibility)42.4724P681RPRE-FURIN0.788 (Stabilizing)?0.066 (Decrease of molecule flexibility)15.3725A701VPOST- FURIN0.192 (Stabilizing)0.033 (Increase of molecule flexibility)2.50-N70326D1163YHR20.365 (Stabilizing)?0.168 (Decrease of molecule flexibility)0.1827G1167VHR2?0.127 (Destabilizing)0.076 (Increase of molecule flexibility)0.13-I1169,+D1163, -D116528V1176FHR2?0.252 (Destabilizing)?0.178 (Decrease of molecule flexibility)2.88 Open in Rabbit Polyclonal to CCDC102B a separate window Open in a separate window Open in a separate window Open in a separate window Open in a separate window Fig.?1 DynaMut prediction of interactomic interactions for only increasing the molecule flexibility, wild-type and mutant residues are coloured in light-green and represented as sticks alongside the surrounding residues involved in any interactions. Table?3 shows the disulphide score (Sss) prediction by another tool, MAESTRO, along the reference sequence of the wild type. The prediction shows that cysteine 743 (C743) with cysteine 749 (C749) appeared as the best two partners to form a disulphide bond, giving the highest negative Sss value of -4.610, at pH?=?7. Any amino acid substitution in these two cysteines would significantly affect the protein folding verified by the prediction tool; Phyre2 gives high mutational sensitivity (Appendix, Figure?S). We have noticed that some variants of interest are located within the locations of the two disulphide bond partners. For example, E484K or E484Q is situated in the amino sequence C480-NGVEGFN-C488. The disulphide partners with an Sss score of -4.352 where the amino acids acid substitution in that location is expected to increase the spike protein thermodynamic flexibility as shown in the DynaMut results Astragaloside II in Table?2. Other examples include the sites of N439K, Y453F, S477?N, N501Y or N501T, and L452R; the variants located in the amino sequence between C391with C525 the disulphide partners with Sss score of??2.653 where the amino acid substitution in these two locations are expected to decrease the spike protein thermodynamic flexibility as shown in the DynaMut results in Table?2. Table?3 Disulfide score (Sss) prediction by MAESTRO. thead th rowspan=”1″ colspan=”1″ Disulfide bond interaction by MAESTRO /th th rowspan=”1″ colspan=”1″ Sss /th th rowspan=”1″ colspan=”1″ Critical Amino Acid Sequence /th th rowspan=”1″ colspan=”1″ High Astragaloside II mutation by Phyre2 /th /thead C743 with C749?4.610CGDSTECC743, C749C738 with C760?4.536CTMYICGDSTECSNLLLQYGSFCC738, C743, C749, C760C538.with C590?4.528CVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCC538, G550, C590C480 with C488?4.352CNGVEGFNCC480, C488C1082 with C1126?4.320CHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCC1082, P1090, C1126C291.with C301?3.996CALDPLSETKCC291, C301C617.with C649?3.934CTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCC617, C649C662.with C671?3.252CDIPIGAGICC662, C671C131 with C166?3.193CEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCC131, C136, P139,.