Publisher Summary This chapter investigates the anatomy and taxonomy of protein structures. A protein is a polypeptide chain made up of amino acid residues linked together in a definite sequence. Amino acids are “handed,” and naturally occurring proteins contain only L-amino acids. A simple mnemonic for that purpose is the “corncrib.” The sequence of side chains determines all that is unique about a particular protein, including its biological function and its specific three-dimensional structure. The major possible routes to knowledge of three-dimensional protein structure are prediction from the amino acid sequence and analysis of spectroscopic measurements such as circular dichroism, laser Raman spectroscopy, and nuclear magnetic resonance. The analysis and discussion of protein structure is based on the results of three-dimensional X-ray crystallography of globular proteins. The basic elements of protein structures are discussed. The most useful level at which protein structures are to be categorized is the domain, as there are many cases of multiple-domain proteins in which each separate domain resembles other entire smaller proteins. The simplest type of stable protein structure consists of polypeptide backbone wrapped more or less uniformly around the outside of a single hydrophobic core. The outline of the taxonomy is also provided in the chapter.

The anatomy and taxonomy of protein structure.

We present an approach for deriving net atomic charges from ab initio quantum mechanical calculations using a least squares fit of the quantum mechanically calculated electrostatic potential to that of the partial charge model. Our computational approach is similar to those presented by Momany [J. Phys. Chem., 82, 592 (1978)], Smit, Derissen, and van Duijneveldt [Mol. Phys., 37, 521 (1979)], and Cox and Williams [J. Comput. Chem., 2, 304 (1981)], but differs in the approach to choosing the positions for evaluating the potential. In this article, we present applications to the molecules H2O, CH3OH, (CH3)2O, H2CO, NH3, (CH3O)2PO, deoxyribose, ribose, adenine, 9-CH3 adenine, thymine, 1-CH3 thymine, guanine, 9-CH3 guanine, cytosine, 1-CH3 cytosine, uracil, and 1-CH3 uracil. We also address the question of inclusion of “lone pairs,” their location and charge.

An approach to computing electrostatic charges for molecules

It is demonstrated that semiempirical methods give electrostatic potential (ESP) derived atomic point charges that are in reasonable agreement with ab initio ESP charges. Furthermore, we find that MNDO ESP charges are superior to AM1 ESP charges in correlating with ESP charges derived from the 6-31G* basis set. Thus, it is possible to obtain 6-31G* quality point charges by simply scaling MNDO ESP charges. The charges are scaled in a linear (y = Mx) manner to conserve charge. In this way researchers desiring to carry out force field simulations or minimizations can obtain charges by using MNDO, which requires much less computer time than the corresponding 6-31G* calculation.

Atomic charges derived from semiempirical methods

Today, coupled-cluster theory offers the most accurate results among the practical ab initio electronic-structure theories applicable to moderate-sized molecules. Though it was originally proposed for problems in physics, it has seen its greatest development in chemistry, enabling an extensive range of applications to molecular structure, excited states, properties, and all kinds of spectroscopy. In this review, the essential aspects of the theory are explained and illustrated with informative numerical results.

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Coupled-cluster theory in quantum chemistry

Publisher Summary The vibrational spectrum of a molecule is determined by its three-dimensional structure and its vibrational force field. An analysis of this (usually infrared (IR) and Raman) spectrum can therefore provide information on the structure and on intramolecular and intermolecular interactions. The more probing the analysis, the more detailed is the information that can be obtained. Detailed analyses of the vibrational spectra of macromolecules, however, have provided a deeper understanding of structure and interactions in these systems. An important advance in this direction for proteins came with the determination of the normal modes of vibration of the peptide group in N-methylacetamide, and the characterization of several specific amide vibrations in polypeptide systems. Extensive use has been made of spectra-structure correlations based on some of these amide modes, including attempts to determine secondary structure composition in proteins. Polypeptide molecules exhibit many more vibrational frequencies than the amide modes. Over the years, some normal-mode calculations have provided greater insight into the spectra of particular molecules. However, these have often been based on approximate structures or have employed limited force fields. These force fields can now serve as a basis for detailed analyses of spectral and structural questions in other polypeptide molecules. The aim of this chapter is to present these recent developments in the vibrational spectroscopy of peptides, polypeptides, and proteins.

Vibrational spectroscopy and conformation of peptides, polypeptides, and proteins.

It is generally acknowledged that geometrical and conformational properties of biopolymers have an important effect on their biochemical behaviour. It is less easily recognized that these properties depend also on their macromolecular electronic characteristics.The aim of this review is to demonstrate the significance of such macromolecular electronic effects. Particularly useful for this sake is the recently much developed concept of ‘molecular electrostatic potential’ (MEP) (Scrocco & Tomasi, 1973, 1978) by which is defined the electrostatic (Coulomb) potential created in the neighbouring space by the nuclear charges and the eletronic distribution of a molecule.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S0033583500002341

Molecular electrostatic potential of the nucleic acids.

Publisher Summary This chapter provides an overview of the quantum–mechanical work done in conformation of amino acid residues of proteins with the double objective of comparing the results with those of the previous empirical computations and with the constantly and rapidly increasing amount of experimental data. The most extensive applications have been in the field of proteins and their constituents, which exhibit the most significant conformational problems in biochemistry. The conformational properties of amino acid residues and polypeptides may be classified into three categories corresponding broadly to successive stages of development and refinement, and include—(1) empirical computations in the hard sphere approximation, (2) empirical computations in the partitioned potential energy approximation, and (3) quantum–mechanical computations. The best procedure, which allows the determination of the individual molecular orbitals, is the self-consistent field method. In the great majority of theoretical studies—whether empirical or quantum–mechanical—on the conformational properties of polypeptides, proteins, and their constituents the peptide bond has been considered as planar and trans; however, new developments in a number of directions have increased the interest of taking into consideration the possible nonplanarity of the peptide bonds.

Molecular orbital calculations on the conformation of amino acid residues of proteins.

Publisher Summary This chapter focuses on the various tautomeric forms of the fundamental purines. The principal types of tautomeric transformation liable to occur in the most significant group of purines are prototropic tautomerism, amine-imine tautomerism, and lactam-lactim tautomerism. The amine-imine and the lactam-lactim tautomerisms may be coupled with the shift of the “imidazole proton” on the purine skeleton. In polysubstituted derivatives, such as in 8-azaguanine, all the different types of tautomerisms can be intermingled. A number of tautomeric forms of some fundamental purines have been studied quantum mechanically with the help of the standard, semi empirical Huckel approximation of the molecular orbital method. These studies enabled the determination of a number of electronic differences among the tautomers. Although the molecule of purine is generally represented in the form N(9)H in which a hydrogen atom as attached to N-9, tautomeric forms may naturally be considered in which the proton is attached to the other nitrogens of the molecule, yielding the tautomers N(7)H, N(3)H, and N(1)H. Although the majority of biological purines exist essentially as derivatives of the N(9)H tautomer, the crystalline form of purine itself, which consists of long chains of these molecules linked together by single hydrogen bonds, involves the N(7)H tautomer.

Electronic Aspects of Purine Tautomerism

An additive procedure (SIBFA) is developed for the rapid computation of conformational energy variations in very large molecules. The macromolecule is built out of constitutive molecular fragments and the intramolecular energy is computed as a sum of interaction energies between the fragments. The electrostatic and the polarization components are calculated using multicenter multipole expansions of theab initio SCF electron density of the fragments. The repulsion component is obtained as a sum of bond and lone pair interactions. Tests of the procedure on a series of model compounds containing ether oxygens and pyridine-like nitrogens are reported and compared with the results of correspondingab initio SCF calculations. The resulting methodology is compatible with the simultaneous computation of intermolecular interactions.

Theoretical studies of molecular conformation. Derivation of an additive procedure for the computation of intramolecular interaction energies. Comparison with ab initio SCF computations

Alberte Pullman

Papers

Molecular electrostatic potential of the nucleic acids.

Molecular orbital calculations on the conformation of amino acid residues of proteins.

Electronic Aspects of Purine Tautomerism

Theoretical studies of molecular conformation. Derivation of an additive procedure for the computation of intramolecular interaction energies. Comparison with ab initio SCF computations

Les théories électroniques de la chimie organique