The restrained electrostatic potential (RESP) approach is a highly regarded and widely used method of assigning partial charges to molecules for simulations. RESP uses a quantum-mechanical method that yields fortuitous overpolarization and thereby accounts only approximately for self-polarization of molecules in the condensed phase. Here we present RESP2, a next generation of this approach, where the polarity of the charges is tuned by a parameter, δ, which scales the contributions from gas- and aqueous-phase calculations. When the complete non-bonded force field model, including Lennard-Jones parameters, is optimized to liquid properties, improved accuracy is achieved, even with this reduced set of five Lennard-Jones types. We argue that RESP2 with δ ≈ 0.6 (60% aqueous, 40% gas-phase charges) is an accurate and robust method of generating partial charges, and that a small set of Lennard-Jones types is a good starting point for a systematic re-optimization of this important non-bonded term.

受限静电势 (RESP) 方法是一种备受推崇和广泛使用的方法，用于将部分电荷分配给分子进行模拟。RESP 使用一种量子力学方法，该方法会产生偶然的过极化，因此只能近似解释凝聚相中分子的自极化。在这里，我们介绍了 RESP2，这是该方法的下一代，其中电荷的极性由参数 δ 调整，该参数衡量气相和水相计算的贡献。当完整的非键合力场模型（包括 Lennard-Jones 参数）针对液体特性进行优化时，即使使用这五种 Lennard-Jones 类型的简化集，也可以提高精度。我们认为 RESP2 与δ ≈ 0.6（60% 水溶液，40% 气相电荷）是产生部分电荷的准确而稳健的方法，并且一小部分 Lennard-Jones 类型是系统重新优化这一重要非电荷的良好起点- 保税条款。