Disorders in the central nervous system have been ascribed to impairments in the function of the AMPA ionotropic glutamate receptors (iGluRs), which are ligand-gated ion channels that undergo structural changes after activation, mediating fast synaptic transmission in the central nervous system. Experimental, computational, and crystallographic analyses have been used to describe partial agonism in AMPA receptors – mainly those related to the willardiines, namely fluorine–willardiine (FW), hydrogen–willardiine (HW), bromine–willardiine (BrW), and iodine–willardiine (IW). By employing quantum chemistry methods based on the density functional theory approach, we unveil here the detailed binding energy features of willardiines co-crystallized with the iGluRs receptors. Our computational results demonstrate that the total binding energies of the AMPA–Willardiines complex correlate with the agonist binding energies, whose experimental sequential data match our computational counterpart, excluding the HW case. Besides, it was observed that FW, BrW, and IW have significant charged states at physiological pH.

The integration of DNA and RNA nucleobases to improve the performance of organic light-emitting diodes, as a low-cost and environmentally friendly optoelectronic device, has attracted a lot of interest in recent years. As a contribution to an improved understanding of the DNA/RNA-based devices in the solid state, we presented here a dispersion corrected density functional theory (DFT) and time-dependent DFT calculations to obtain the optimized geometries, Kohn-Sham band structures, charge distribution, optical absorption, Frenkel exciton binding energies, and complex dielectric functions of the five DNA/RNA nucleobases anhydrous crystals. Optical absorption measurements on the DNA/RNA nucleobase powders were also performed for comparison with the simulations. Effective masses for the carriers were calculated, indicating that the guanine and the cytosine crystals have potential applications in optoelectronics as a direct gap semiconductor, with the other nucleobases (adenine, thymine, and uracil) presenting either a semiconductor or an insulator character, depending on the carrier type.

We present a quantum chemistry simulation to discuss the binding energy features of different methodologies in the fight against cancer. In the first one, selective estrogen receptor modulators used in breast cancer treatment are considered co-crystallized with estrogen receptors. Our theoretical binding energies and the experimental one are compared, and their features are discussed. Then, we investigate the importance of integrins in several cell types that affect tumor progression. In particula,r its binding energy features with cilengitide is investigated and proved to be an efficient alternative toward the development of new drugs. Finally, we discuss the efficiency of immunotherapy as a promising new cancer treatment. By reawakening and enhancing the immune system to fight cancer, this strategy has achieved impressive clinical responses. Much of them have been generated by the recognition that immune checkpoint proteins, like the PD-1 receptor, can be blocked by antibody-based drugs with profound effects.

Using an effective tight-binding model, together with a transfer matrix technique, we investigate the electronic transport through oligopeptide chains, such as amino acid pairs and the Alpha3-helical polypeptide and its variants, sandwiched between two platinum electrodes. Our results show that factors such as the oligopeptide chain length and the possible combinations between the amino acids residues are crucial to the electronic conductance profiles. The temperature dependence of the electronic specific heat at constant volume spectra are also depicted. Applying our findings to single-stranded microRNAs (miRNAs) chains, which are associated to autism disorder, a relationship between the current intensity and the autism-related miRNA bases sequences is detected, suggesting that a kind of electronic biosensor can be developed to distinguish different profiles of autism spectrum disorders.

The administration of levodopa/carbidopa, prodrugs that cross the blood–brain barrier and are metabolized to dopamine in the central nervous system, remains the most effective treatment for Parkinson’s disease. The development of carrier systems to increase the rate of blood–brain barrier crossing has been a challenge. In particular, buckminsterfullerene C60 is promising, due to its ability to penetrate through the skin and the gastrointestinal tract. Aiming to give theoretical support to attempts in developing levodopa/carbidopa preparations for transdermal and oral administration looking for more continuous dopamine stimulation, we present a computational study of them adsorbed on C60 fullerene in the 2–8 pH range. We use classical and quantum simulations as our computational tools. Annealing calculations were performed to explore the space of their molecular configurations to obtain optimal geometries. A detailed interpretation of their harmonic vibrational frequencies are also presented, through the analysis of their Raman and infrared spectra.

We present a model describing the electrical conductivity and the current–voltage (IxV) characteristics along DNA finite segments within a tight-binding Hamiltonian model. To mimic the DNA molecule, we consider first a dangling backbone ladder (DBL)-DNA Poly(CG) sequences, whose building blocks are the bases cytosine and guanine. We found that the long-range (short-range) character of the correlations is important to the transmissivity spectra (IxV curves). Afterward, we investigate a Poly(CG-CT) DNA segment with diluted base pairing restricted to occur at a fraction p of the cytosine nucleotides, at which a guanine nucleotide is attached. We show that the effective disorder introduced by the diluted base pairing is much stronger in poly(CG) than in poly(CT) segments, with significant consequences for the electronic transport properties. Finally, methylated DNA strands sandwiched between two metallic electrodes are considered, whose IxV curves suggest potential applications in the development of novel biosensors for molecular diagnostics.

Ascorbic acid (AsA) and the nonsteroidal anti-inflammatory drug ibuprofen (IBU), adsorbed noncovalently on buckminsterfullerene C60 for its transdermal delivery, are investigated using Classical Molecular Dynamics and Density Functional Theory. Classical annealing is performed to explore the molecular configurations of both AsA and IBU adsorbed on C60, searching for optimal geometries. In particular, it is shown that IBU assumes two distinct adsorption geometries, giving rise to a two-level adsorption, leading to an extended anti-inflammatory delivery time. A vibrational analysis was also carried out for adsorbed IBU, depicting the IR and Raman spectra for both geometries. Furthermore, we investigated also the binding of IBU to human serum albumin (HSA) by using a fragmentation strategy together with a dispersion corrected exchange–correlation functional. Our computer simulations are valuable for a better understanding of the binding mechanism of AsA and IBU, looking for rational design and the development of novel drugs with improved potency.

Collagen-based biomaterials are expected to become a useful matrix substance for various biomedical applications in the future. By taking advantage of the crystallographic data of the triple-helical peptide T3-785, a collagen-like peptide whose homotrimeric structure presents large conformational similarity to the human type III collagen, we present a quantum chemistry study to unveil its detailed binding energy features and conformation stability, considering the inter-chain interaction energies of 90 amino acid residues distributed into three interlaced monomers. Our theoretical model is based on the density functional theory formalism within the molecular fragmentation with conjugate caps approach. We present also its interaction with the integrin, a collagen receptor that facilitates cell-extracellular matrix adhesion, looking for the development and synthesis of artificial collagen with high stability for bioengineering applications. Besides, we depicted the relevance of each strand in the triple-helical collagen structure, helping the understanding of the events involving the integrin–collagen complex interaction energy.

We performed a theoretical study of the specific heat, as a function of the temperature, for double-strand DNA quasiperiodic sequences. The energy spectra are calculated using the 2-D Schrödinger equation, in a tight-binding approximation, with the on-site energy exhibiting long-range disorder and nonrandom hopping amplitudes. Classical, quantum, and nonextensive statistics are taken into account to perform the specific heat spectra. Comparisons are made with finite segment of natural DNA, as part of the human chromosome Ch22. Furthermore, we consider the effects of the solvent interaction on the nonlinear dynamical structure of a DNA segment, by using a time-independent perturbation approach, to investigate the denaturation temperature profiles of some DNA’s thermodynamic functions, such as the stretching of the hydrogen bonds, the specific heat, and the entropy. Besides a sharp thermal profile behavior of these functions, we also observe that the DNA’s melting temperature decreases as the solvent potential increases.

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.