The steady increase in computational power in the last 50 years is opening unprecedented opportunities in biology, as computer simulations of biological systems have become more accessible and can reproduce experimental results more accurately. Here, we wanted to test the ability of computer simulations to replace experiments in the limited but practically useful scope of improving the biochemical characteristics of the abN48 antibody, a nanomolar antagonist of the CXC chemokine receptor 2 (CXCR2) that was initially selected from a combinatorial antibody library. Our results showed a good correlation between the computed binding energies of the antibody to the peptide target and the experimental binding affinities. Moreover, we showed that it is possible to design new antibody sequences in silico with a higher affinity to the desired target using a Monte Carlo Metropolis algorithm. The newly designed sequences had an affinity comparable to the best ones obtained using in vitro affinity maturation and could be obtained within a similar timeframe. The methodology proposed here could represent a valid alternative for improving antibodies in cases in which experiments are too expensive or technically tricky and could open an opportunity for designing antibodies for targets that have been elusive so far.
Keywords: CXCR2; MM-PBSA (Molecular Mechanic/Poisson-Boltzmann Surface Area); in silico affinity maturation; monoclonal antibodies.