He corresponding CLIP peptide, and to interact with the sameFigure two Modeling of your interaction between HLA-DRB1*03:01, SLA/LP452-465, and PS 120790-804. A) The crystal structure of HLA-DRB1*03:01 is represented as ribbons and transparent surface, with carbon atoms colored in light grey, oxygen in red, nitrogen in blue and sulfur in yellow. SLA/LP452-465 (peptide “A”) and PS 120790-804 (peptide “B”) are depicted as cyan and brown sticks, respectively. The location of anchoring pockets P1, P4, P6 and P9 is also indicated. B) Detail from the P4 binding cleft. This figure was rendered with PyMOL [35].Paiardini and Pascarella Theoretical Biology and Medical Modelling 2013, 10:25 http://tbiomed/content/10/1/Page six offunctional residues. Particular care was taken to eliminate the steric clashes within the resulting complex. After manual docking and power minimization from the complexes, peptide “A” and “B” showed excellent predicted binding affinities for HLA-DRB1*03:01 (-33.six Kcal/mol for peptide “A” and -28.1 Kcal/mol for peptide “B”). Both peptides twist inside the typical kind II polyproline helix, using the sequestration of peptide side chains in polymorphic P1, P4, P6, and P9 pockets inside the HLA protein, which have been identified as key anchors [33]. Table 1 reports the receptor-ligand residue free of charge energy contacts for HLA-DRB1*03:01-peptide “A” and HLA-DRB1*03:01-peptide “B” complexes. As anticipated, residue Leu 454 of peptide “A” (Leu 792 of peptide “B”) fits properly within the extremely hydrophobic P1 pocket, formed by residues Phe 24, Ile 31, Phe 32, Trp 43, Ala 52, Asn 82, Val 85, Val 86 and Phe 89 of HLA-DRB1*03:01 (predicted desolvation cost-free energy: -5.624 Kcal/mol and -5.440 for peptide “A” and “B”, respectively). In accordance with Table 1, a “hot spot” of interaction in between HLA-DRB1*03:01 and peptide “B” is located at the P4 binding pocket, and is represented by the salt bridges involving Lys at position 71 and Arg at position 74 in the HLA protein, and Glu 795 of PS120 peptide (Lys 71-Glu 795, -5.191 Kcal/mol; Arg 74-Glu 795, -3.153 Kcal/mol). These interactions will not be present in SLA/LP immunodominant peptide, where the Glu residue is substituted for Cys 457. The P6 binding pocket of HLA-DRB1* 03:01 is negatively charged, becoming occupied by residues Glu 9 of chain A, Glu 11 and Asp 66 of chain B. In this pocket are accommodated the positively charged residue LysTable 1 Best ten hot spots of interaction (in accordance with no cost energy of binding) amongst HLA-DRB1*03:01, human SLA/LP452-465, plus the corresponding PS 120790-804 from R. prowazekiiHLA-DRB1*03:01 Asp B57 Glu A55 Asp A66 Glu B9 Arg A76 Leu B53 Ser B11 Tyr B78 Val B85 Phe A54 HLA-DRB1*03:01 Lys B71 Asp A66 Arg B74 Glu B9 Arg B74 Asp B57 Tyr B61 Glu A55 Phe A54 Val B85 SLA/LP Arg 462 Arg 453 Lys 459 Lys 549 Arg 465 Arg 462 Lys 459 Cys 457 Leu 454 Leu 454 PS 120 Glu 795 Lys 797 Glu 795 Lys 797 Leu 796 Asn 800 Ile 801 Arg 794 Leu 792 Leu 792 No cost power (Kcal/mol) -7.Formula of 103031-30-7 382 -5.(S)-(+)-Norepinephrine L-bitartrate Data Sheet 015 -4.PMID:33547137 108 -2.518 -2.381 -2.013 -1.879 -1.158 -1.130 -1.081 Free of charge energy (Kcal/mol) -5.191 -3.279 -3.153 -2.671 -1.972 -1.425 -1.235 -1.211 -1.121 -1.Paiardini and Pascarella Theoretical Biology and Health-related Modelling 2013, 10:25 http://tbiomed/content/10/1/Page 7 ofand Lys 797 of peptides “A” and “B”, respectively, which favourably contribute for the cost-free power of binding (-3.609 Kcal/mol and -4.072 Kcal/mol, respectively). Lastly, the positively charged side-chain of Arg 462 of peptide “A” is situated inside the P9 binding pocket, exactly where it in.