ICOSA: A Distance-Dependent, Orientation-Specific Coarse-Grained Contact Potential for Protein Structure Modeling

•Correlating inter-residue contact distance and orientation in icosahedral local coordinates to evaluate pair-wise inter-residue interactions.•Finite ideal gas reference state in icosahedral local coordinates.•Better than widely used coarse-grained potentials and comparable to popular all-atom potentials in identifying correct models.

The relative distance and orientation in contacting residue pairs plays a significant role in protein folding and stabilization. We hereby devise a new knowledge-based, coarse-grained contact potential, so-called ICOSA, by correlating inter-residue contact distance and orientation in evaluating pair-wise inter-residue interactions. The rationale of our approach is to establish icosahedral local coordinates to estimate the statistical residue contact distributions in all spherical triangular shells within a sphere. We extend the theory of finite ideal gas reference state to icosahedral local coordinates. ICOSA incorporates long-range contact interactions, which is critical to ICOSA sensitivity and is justified in statistical rigor. With only backbone atoms information, ICOSA is at least comparable to all-atom, fine-grained potentials such as Rosetta, DFIRE, I-TASSER, and OPUS in discriminating near-natives from misfold protein conformations in the Rosetta and I-TASSER protein decoy sets. ICOSA also outperforms a set of widely used coarse-grained potentials and is comparable to all-atom, fine-grained potentials in identifying CASP10 models.

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