Proton decay is a major prediction of Grand-Unified Theories (GUT) and its observation would indicate baryon number violation that is required for baryogenesis. Many decades of searching for proton decay have constrained its rate and ruled out some of the simplest GUT models. Apart from the baryon number-violating interactions, this rate also depends on transition amplitudes between the proton and mesons or leptons produced in the decay, which are matrix elements of three-quark operators. We report nonperturbative calculation of these matrix elements for the most studied two-body decay channels into a meson and antilepton done on a lattice with physical light and strange quark masses and lattice spacings $a\approx0.14$ and $0.20$ fm. We perform nonperturbative renormalization and excited state analysis to control associated
systematic effects. Our results largely agree with previous lattice calculations done with heavier quark masses and thus remove ambiguity in ruling out some simple GUT theories due to quark mass dependence of hadron structure.