We present the foundations of quantum mechanics required to describe atoms and molecules. Starting from classical mechanics, Schrödinger’s equation is introduced, while many-particle systems are approached using the Hartree and Hartree-Fock methods. Different chemical bond types are discussed in this context, namely: ionic, covalent, hydrogen, and van der Waals bonds. Classical molecular dynamics calculations are shown to be employed in the investigation of systems with up to millions of atoms, but quantum-level calculations are essential for an accurate description of chemical bond breaking and formation in biomolecular systems. The essentials of density functional theory (DFT), detailing the Hohenberg-Kohn theorems and the Kohn-Sham strategy, are presented. Distinct exchange-correlation functional approximations are shown with their limitations and advantages, including hybrid functionals. Finally, the description of a fragmentation strategy to apply quantum methods in the study of protein–ligand interactions is discussed.

A discussion on the relevance of protein–protein interactions (PPIs) in biochemistry and biophysics is presented, with the definitions of the proteome, interactome, and the classification of the PPIs. In particular, the essential role played by the Protein Data Bank (PDB) for the study of the PPIs is highlighted, as well as the use of classical molecular dynamics to improve the quality of PDB data and to test novel ligand geometries to improve drug efficiency. Focusing directly on the theoretical description of PPIs using physics, a detailed assessment of the dielectric function of proteins is carried out, with the definition of homogeneous and inhomogeneous dielectric constants and the description of the hydration layer of a solvated protein. Three strategies for the description of the inhomogeneous dielectric constant of proteins are shown, and a fragmentation procedure using density function theory (DFT) to obtain detailed energetic profiles of PPIs is depicted.

Considering the crystallographic data of the Human HMG-CoA reductase (HMGR) complexed with statins, a quantum chemistry study, based on the density functional theory, is performed to estimate the interaction energy for each statin, when one considers binding pockets of different sizes, based solely on the interpretation of crystallographic data of the HMGR–statin complex. Assuming a correlation between the statin potency and the strength of the HMGR–statin binding energies, clinical data of these cholesterol-lowering drugs are successfully explained after stabilization of the calculated binding energy for a larger size of the ligand-interacting HMGR region. The statins atorvastatin and rosuvastatin are shown to be the most strongly bound HMGR inhibitors, while simvastatin and fluvastatin are the weakest ones. An accurate description of the residue–ligand interaction energies at the binding site suggests a quantum chemistry–based route for the development of new statin derivatives.

Computational quantum chemistry is one of the most successful techniques to calculate the main properties of molecules and solids. It is also widely used in the design of new pharmaceutical drugs and biological materials. In general, it is based entirely on quantum mechanics and its basic physical constants, the so-called ab initio method. Usually, the unveiling of the DNA molecule, as well as the secondary structure (alpha-helix and beta-sheet) in proteins, in the 1950s, together with other relevant breakthrough discoveries, marked its dawn. Since then, many achievements in biology, chemistry, physics, and pharmaceutical science were obtained, leading to its solid reputation as a primer tool now available to scientists. It allows investigations with greater accuracy and at an unprecedented level of detail, leading not only to the ability to make a direct comparison with experimental data but also even to predict hitherto unobservedimportant phenomena.

Density functional theory computations within the local density approximation and generalized gradient approximation, in pure form and with dispersion correction, were carried out to investigate the structural, electronic, and optical properties of several amino acid anhydrous crystals. The electronic (band structure and density of states) and optical absorption properties were used to interpret the light absorption measurements performed at room temperature. Mulliken and Hirshfeld population analysis were also performed to assess the degree of charge polarization in the zwitterion state of some amino acid molecules in the DFT converged crystal. Different dielectric function profiles obtained for some of the most important symmetry directions also demonstrate the optical anisotropy of the amino acid anhydrous crystals. The infrared absorption and Raman scattering spectra were recorded and interpreted, with their normal modes assigned. The complex role of water on the carrier transport properties in the monohydrated aspartic acid crystals is also highlighted.

We use a tight-binding formulation to investigate the electronic density of states and the energy spectra of single and double-strand DNA molecules made up from the nucleotides guanine (G), adenine (A), cytosine (C), and thymine (T). A renormalization group approach is also employed to take into account the sugar–phosphate contribution. In order to reveal the relevance of the underlying correlations in the nucleotides distribution, we compare the results for the genomic DNA sequence with those of two artificial quasiperiodic sequences: the Fibonacci and Rudin-Shapiro ones, which have long-range correlations. In addition, we consider also a random sequence, which is a kind of prototype of a short-range correlated system, presented here with the same first-neighbor pair correlations of the human DNA sequence. We found that the long-range character of the correlations is important to the persistence of resonances of finite segments.

Since the early days of migrainous research, serotonin receptors have been considered a major target of drugs, being among the most marketed one for its treatment. They are also involved in the mechanisms underlying many neurological dysfunctions. In this context, by taking advantage of their crystallographic structure co-crystallized with their agonist dihydroergotamine (DHE), one of the oldest and most widely used antimigraine drugs, a quantum chemistry study based on the electrostatically embedded molecular fractionation with conjugate caps scheme within the density functional theory formalism is performed to unveil this complex’s detailed binding energy. Furthermore, we predict the relevance of the DHE regions, as well as the influence of each protein segment to DHE–serotonin receptor binding. We believe that our work is a first step using in silico quantum design as a means to influence the discovery of new drugs to treat migraine and other diseases related to the serotonin agonist.