ConspectusThe quantum chemical modeling of organic crystals and other molecular condensed-phase problems requires computationally affordable electronic structure methods which can simultaneously describe intramolecular conformational energies and intermolecular interactions accurately. To achieve this, we have developed a spin-component-scaled, dispersion-corrected second-order Møller-Plesset perturbation theory (SCS-MP2D) model. SCS-MP2D augments canonical MP2 with a dispersion correction which removes the uncoupled Hartree-Fock dispersion energy present in canonical MP2 and replaces it with a more reliable coupled Kohn-Sham treatment, all evaluated within the framework of Grimme's D3 dispersion model. The spin-component scaling is then used to improve the description of the residual (nondispersion) portion of the correlation energy.The SCS-MP2D model improves upon earlier corrected MP2 models in a few ways. Compared to the highly successful dispersion-corrected MP2C model, which is based solely on intermolecular perturbation theory, the SCS-MP2D dispersion correction improves the description of both inter- and intramolecular interactions. The dispersion correction can also be evaluated with trivial computational cost, and nuclear analytic gradients are computed readily to enable geometry optimizations. In contrast to earlier spin-component scaling MP2 models, the optimal spin-component scaling coefficients are only mildly sensitive to the choice of training data, and a single global parametrization of the model can describe both thermochemistry and noncovalent interactions.The resulting dispersion-corrected, spin-component-scaled MP2 (SCS-MP2D) model predicts conformational energies and intermolecular interactions with accuracy comparable to or better than those of many range-separated and double-hybrid density functionals, as is demonstrated on a variety of benchmark tests. Among the functionals considered here, only the revDSD-PBEP86-D3(BJ) functional gives consistently smaller errors in benchmark tests. The results presented also hint that further improvements of SCS-MP2D may be possible through a more robust fitting procedure for the seven empirical parameters.To demonstrate the performance of SCS-MP2D further, several applications to molecular crystal problems are presented. The three chosen examples all represent cases where density-driven delocalization error causes GGA or hybrid density functionals to artificially stabilize crystals exhibiting more extended π-conjugation. Our pragmatic strategy addresses the delocalization error by combining a periodic density functional theory (DFT) treatment of the infinite lattice with intramolecular/conformational energy corrections computed with SCS-MP2D. For the anticancer drug axitinib, applying the SCS-MP2D conformational energy correction produces crystal polymorph stabilities that are consistent with experiment, in contrast to earlier studies. For the crystal structure prediction of the ROY molecule, so named for its colorful red, orange, and yellow crystals, this approach leads to the first plausible crystal energy landscape, and it reveals that the lowest-energy polymorphs have already been found experimentally. Finally, in the context of photomechanical crystals, which transform light into mechanical work, these techniques are used to predict the structural transformations and extract design principles for maximizing the work performed.