Integrating All-Atom and Coarse-Grained Simulations—Toward Understanding of IDPs at Surfaces

Abstract

We present a scheme for transferring conformational degrees of freedom from all-atom (AA) simulations of an intrinsically disordered protein (IDP) to coarse-grained (CG) Monte Carlo (MC) simulations using conformational swap moves. AA simulations of a single histatin 5 peptide in water were used to obtain a structural ensemble, which is reweighted in a CGMC simulation in the presence of a negatively charged surface. For efficient sampling, the AA trajectory was condensed using two approaches: RMSD clustering (based on the root-mean-square difference in atom positions) and a "naıve" truncation, where only every 100th frame of the trajectory was included in the library. The results show that even libraries with few structures well reproduce the radius of gyration and interaction free energy as functions of the distance from the surface. We further observe that the surface slightly promotes the secondary structure of histatin 5 and more so if using explicit surface charges rather than smeared charges.

On the interactions of the receptor-binding domain of SARS-CoV-1 and SARS-CoV-2 spike proteins with monoclonal antibodies and the receptor ACE2

“…The term ε LJ regulates the strength of the attractive forces in the system (Poveda-Cuevas et al, 2020; Barroso da Silva et al, 2016; Delboni and Barroso da Silva, 2016). Typically, ε LJ is assumed to be universal for any biomolecular system and equals to 0.124 kJ/mol (Barroso da Silva et al, 2016; Delboni and Barroso da Silva, 2016; Persson et al, 2010;Hyltegren et al, 2020). This should correspond to a Hamaker constant of ca.…”

“…However, this value might result in both an over or an underestimation of the attraction depending on the biomolecular system (Barroso da Silva et al, 2016; Delboni and Barroso da Silva, 2016; Hyltegren et al, 2020). For instance, ε LJ equals to 1.7k B T (a value 34 times greater than 0.124 kJ/mol) was necessary to reproduce experimental data for the histatin-5 adsorption to a hydrophilic silica surface (Hyltegren et al, 2020). Conversely, the?…”

On the interactions of the receptor-binding domain of SARS-CoV-1 and SARS-CoV-2 spike proteins with monoclonal antibodies and the receptor ACE2

“…27,42,43 Typically, εLJ is assumed to be universal for any biomolecular system and equals to 0.124 kJ/mol. 42,43,53,62 This should correspond to a Hamaker constant of ca. 9kBT (kB = 1.380×10 -23 m 2 kgs -2 K -1 is the Boltzmann constant, and T is the temperature in Kelvin) for amino acid pairs.…”

“…43,53,63 However, this value might result in both an over or an underestimation of the attraction depending on the biomolecular system. 42,43,62 For instance, εLJ equals to 1.7kBT (a value 34 times greater than 0.124 kJ/mol) was necessary to reproduce experimental data for the histatin-5 adsorption to a hydrophilic silica surface. 62 Conversely, the -lactoglobulin-lactoferrin complexation seems to be overestimated by the usual value of εLJ.…”

“…42,43,62 For instance, εLJ equals to 1.7kBT (a value 34 times greater than 0.124 kJ/mol) was necessary to reproduce experimental data for the histatin-5 adsorption to a hydrophilic silica surface. 62 Conversely, the -lactoglobulin-lactoferrin complexation seems to be overestimated by the usual value of εLJ. 43 Consequently, our research strategy has been to adopt the consensus value of 0.05kBT (= 0.124 kJ/mol) for εLJ.…”