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• W4353032304 abstract "Abstract The evolutionary and functional studies suggested that the emergence of the Omicron variants can be determined by multiple fitness trade-offs including the immune escape, binding affinity for ACE2, conformational plasticity, protein stability and allosteric modulation. In this study, we systematically characterize conformational dynamics, protein stability and binding affinities of the SARS-CoV-2 Spike Omicron complexes with the host receptor ACE2 for BA.2, BA.2.75, XBB.1 and XBB.1.5 variants. We combined multiscale molecular simulations and dynamic analysis of allosteric interactions together with the ensemble-based mutational scanning of the protein residues and network modeling of epistatic interactions. This multifaceted computational study characterized molecular mechanisms and identified energetic hotspots that can mediate the predicted increased stability and the enhanced binding affinity of the BA.2.75 and XBB.1.5 complexes. The results suggested a mechanism driven by the stability hotspots and a spatially localized group of the Omicron binding affinity centers, while allowing for functionally beneficial neutral Omicron mutations in other binding interface positions. A network-based community model for the analysis of non-additive epistatic contributions in the Omicron complexes is proposed revealing the key role of the binding hotspots R498 and Y501 in mediating community-based epistatic couplings with other Omicron sites and allowing for compensatory dynamics and binding energetic changes. The results also showed that mutations in the convergent evolutionary hotspot F486 can modulate not only local interactions but also rewire the global network of local communities in this region allowing the F486P mutation to restore both the stability and binding affinity of the XBB.1.5 variant which may explain the growth advantages over the XBB.1 variant. The results of this study are consistent with a broad range of functional studies rationalizing functional roles of the Omicron mutation sites that form a coordinated network of hotspots enabling balance of multiple fitness tradeoffs and shaping up a complex functional landscape of virus transmissibility." @default.
• W4353032304 created "2023-03-23" @default.
• W4353032304 creator A5023698777 @default.
• W4353032304 creator A5031922505 @default.
• W4353032304 creator A5088855335 @default.
• W4353032304 date "2023-03-22" @default.
• W4353032304 modified "2023-10-17" @default.
• W4353032304 title "Balancing Functional Tradeoffs between Protein Stability and ACE2 Binding in the SARS-CoV-2 Omicron BA.2, BA.2.75 and XBB Lineages : Dynamics-Based Network Models Reveal Epistatic Effects Modulating Compensatory Dynamic and Energetic Changes" @default.
• W4353032304 cites W1948562438 @default.
• W4353032304 cites W1968454533 @default.
• W4353032304 cites W1972758026 @default.
• W4353032304 cites W1989925383 @default.
• W4353032304 cites W2001296212 @default.
• W4353032304 cites W2023490488 @default.
• W4353032304 cites W2030114807 @default.
• W4353032304 cites W2031616354 @default.
• W4353032304 cites W2038758364 @default.
• W4353032304 cites W2042332534 @default.
• W4353032304 cites W2047849624 @default.
• W4353032304 cites W2050333027 @default.
• W4353032304 cites W2074002527 @default.
• W4353032304 cites W2090264443 @default.
• W4353032304 cites W2101414808 @default.
• W4353032304 cites W2106648157 @default.
• W4353032304 cites W2109441358 @default.
• W4353032304 cites W2111270835 @default.
• W4353032304 cites W2113557726 @default.
• W4353032304 cites W2117541321 @default.
• W4353032304 cites W2150981663 @default.
• W4353032304 cites W2151936673 @default.
• W4353032304 cites W2156620408 @default.
• W4353032304 cites W2158562723 @default.
• W4353032304 cites W2163641424 @default.
• W4353032304 cites W2164928285 @default.
• W4353032304 cites W2165533101 @default.
• W4353032304 cites W2167686614 @default.
• W4353032304 cites W2170060741 @default.
• W4353032304 cites W2172034373 @default.
• W4353032304 cites W2174592307 @default.
• W4353032304 cites W2207783648 @default.
• W4353032304 cites W2344557669 @default.
• W4353032304 cites W2345331290 @default.
• W4353032304 cites W2411913461 @default.
• W4353032304 cites W2512372054 @default.
• W4353032304 cites W2544136853 @default.
• W4353032304 cites W2555870966 @default.
• W4353032304 cites W2577347274 @default.
• W4353032304 cites W2587638657 @default.
• W4353032304 cites W2797118818 @default.
• W4353032304 cites W2890113953 @default.
• W4353032304 cites W2981507824 @default.
• W4353032304 cites W3007500173 @default.
• W4353032304 cites W3007643904 @default.
• W4353032304 cites W3009335299 @default.
• W4353032304 cites W3011537081 @default.
• W4353032304 cites W3015190630 @default.
• W4353032304 cites W3035128829 @default.
• W4353032304 cites W3042332408 @default.
• W4353032304 cites W3044914269 @default.
• W4353032304 cites W3045149055 @default.
• W4353032304 cites W3046414208 @default.
• W4353032304 cites W3047461618 @default.
• W4353032304 cites W3048714202 @default.
• W4353032304 cites W3058836816 @default.
• W4353032304 cites W3087347658 @default.
• W4353032304 cites W3089840021 @default.
• W4353032304 cites W3095499424 @default.
• W4353032304 cites W3103843063 @default.
• W4353032304 cites W3108980364 @default.
• W4353032304 cites W3124262119 @default.
• W4353032304 cites W3125256861 @default.
• W4353032304 cites W3125912401 @default.
• W4353032304 cites W3126119092 @default.
• W4353032304 cites W3138278914 @default.
• W4353032304 cites W3157679298 @default.
• W4353032304 cites W3157697503 @default.
• W4353032304 cites W3162006159 @default.
• W4353032304 cites W3164917922 @default.
• W4353032304 cites W3168708929 @default.
• W4353032304 cites W3193526107 @default.
• W4353032304 cites W3193682077 @default.
• W4353032304 cites W3195039506 @default.
• W4353032304 cites W3201038556 @default.
• W4353032304 cites W3208696217 @default.
• W4353032304 cites W4205331651 @default.
• W4353032304 cites W4206153788 @default.
• W4353032304 cites W4206737621 @default.
• W4353032304 cites W4206898072 @default.
• W4353032304 cites W4210599223 @default.
• W4353032304 cites W4210943449 @default.
• W4353032304 cites W4212851383 @default.
• W4353032304 cites W4213002013 @default.
• W4353032304 cites W4213003635 @default.
• W4353032304 cites W4213222685 @default.
• W4353032304 cites W4214735462 @default.
• W4353032304 cites W4220663942 @default.
• W4353032304 cites W4220680013 @default.
• W4353032304 cites W4220807057 @default.
• W4353032304 cites W4220861013 @default.
• W4353032304 cites W4220900149 @default.

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