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

Carolina Corrêa Giron; Aatto Laaksonen; Fernando L. Barroso da Silva

The electrostatic interactions[ ( )] between any two ionizable amino acids of valences and are given by: Protein-protein interactions are also controlled by other physical contributions (van der Waals interactions, hydrophobic effect, and excluded volume repulsion). 27, 42, 43 A simple and effective way to include their effects is by means of a LJ term [uvdw(rij)] between the beads (amino acids). 27 Mathematically, for any two beads (charged or neutral ones) i and j, uvdw(rij) is given by 6 ], [2] where σij (= Ri + Rj) is the separation distance of two amino acids i and j at contact. For instance, σij for the pair VAL-GLU is 7.2Å (= RVAL + RGLU, where RVAL = 3.4Å and RGLU = 3.8Åsee ref. 53 ). The possibility to use different sizes for these beads allows the incorporation of non-. CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.05.026377 doi: bioRxiv preprint specific contributions from the hydrophobic effect in the model. 43 This should preserve the macromolecular hydrophobic moments 61 and contributes to guide a correct docking orientation at short separation distances. 27 The term εLJ regulates the strength of the attractive forces in the system. 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. 43 Consequently, our research strategy has been to adopt the consensus value of 0.05kBT (= 0.124 kJ/mol) for εLJ. This also implies that the outcomes should be interpreted with relative caution bearing in mind all the intrinsic approaches assumed in the modeling. The direct impact is seen in the free energy derivatives as discussed later at the results section.