KinFams: De-Novo Classification of Protein Kinases Using CATH Functional Units

Protein kinases are important targets for treating human disorders, and they are the second most targeted families after G-protein coupled receptors. Several resources provide classification of kinases into evolutionary families (based on sequence homology); however, very few systematically classify functional families (FunFams) comprising evolutionary relatives that share similar functional properties. We have developed the FunFam-MARC (Multidomain ARchitecture-based Clustering) protocol, which uses multi-domain architectures of protein kinases and specificity-determining residues for functional family classification. FunFam-MARC predicts 2210 kinase functional families (KinFams), which have increased functional coherence, in terms of EC annotations, compared to the widely used KinBase classification. Our protocol provides a comprehensive classification for kinase sequences from >10,000 organisms. We associate human KinFams with diseases and drugs and identify 28 druggable human KinFams, i.e., enriched in clinically approved drugs. Since relatives in the same druggable KinFam tend to be structurally conserved, including the drug-binding site, these KinFams may be valuable for shortlisting therapeutic targets. Information on the human KinFams and associated 3D structures from AlphaFold2 are provided via our CATH FTP website and Zenodo. This gives the domain structure representative of each KinFam together with information on any drug compounds available. For 32% of the KinFams, we provide information on highly conserved residue sites that may be associated with specificity.Adeyelu T, Bordin N, Waman VP, Sadlej M, Sillitoe I, Moya-Garcia AA, Orengo CA. KinFams: De-Novo Classification of Protein Kinases Using CATH Functional Units. Biomolecules. 2023; 13(2):277. https://doi.org/10.3390/biom1302027

Time dependent density functional theory calculation of van der Waals coefficient C6_{6} of alkali-metal atoms Li, Na, K, alkali dimers Li2_{2}, Na2_{2}, K2_{2} and sodium clusters Nan_{n}

In this paper we employ all-electron time dependent density functional theory (TDDFT) to calculate the long range dipole-dipole dispersion coefficient (van der Waals coefficient) $C_{6}$ of alkali-metal atoms Li, Na, K, alkali-metal atom dimers Li$_{2}$, Na$_{2}$, K$_{2}$ and sodium clusters containing even number of atoms ranging from 2 to 20 atoms. The dispersion coefficients are obtained via Casimir-Polder expression which relates it to the frequency dependent linear polarizabilty at imaginary frequencies. The frequency dependent polarizabilities are calculated by employing TDDFT--based complete sum-over-states expressions for the atoms, and direct TDDFT linear response theory for the closed shell dimers and clusters.Comment: 14 pages of text and 4 figure

Deuterated molecules as a probe of ionization fraction in dense interstellar clouds

Deuterium fractionation in molecular ions, in particular HCO+, has been extensively used to estimate the degree of ionization in molecular clouds. This paper reviews recent work on ionization degree in homogeneous clouds. We will show that the N(DCO+)/N(HCO+) column density ratio furnishes a measurement of x(e) only in regions where CO is not significantly depleted, thus in the outer skirts of dense cloud cores. To probe x(e) deep inside the clouds, one has to gauge deuterium enhancement in molecular ions with parent species not affected by depletion (e.g. N2H+), and rely on chemical models which take into account the cloud density structure. Unlike N(DCO+)/N(HCO+), the N(N2D+)/N(N2H+) column density ratio is predicted to considerably increase with core evolution (and/or the amount of CO depletion), reaching large values (> 0.2) in cloud cores on the verge of forming a star.Comment: 25 pages, 5 figures, accepted for publication in the special issue on "Deuterium in The Universe" of Planetary and Space Scienc

Ab initio studies of structures and properties of small potassium clusters

We have studied the structure and properties of potassium clusters containing even number of atoms ranging from 2 to 20 at the ab initio level. The geometry optimization calculations are performed using all-electron density functional theory with gradient corrected exchange-correlation functional. Using these optimized geometries we investigate the evolution of binding energy, ionization potential, and static polarizability with the increasing size of the clusters. The polarizabilities are calculated by employing Moller-Plesset perturbation theory and time dependent density functional theory. The polarizabilities of dimer and tetramer are also calculated by employing large basis set coupled cluster theory with single and double excitations and perturbative triple excitations. The time dependent density functional theory calculations of polarizabilities are carried out with two different exchange-correlation potentials: (i) an asymptotically correct model potential and (ii) within the local density approximation. A systematic comparison with the other available theoretical and experimental data for various properties of small potassium clusters mentioned above has been performed. These comparisons reveal that both the binding energy and the ionization potential obtained with gradient corrected potential match quite well with the already published data. Similarly, the polarizabilities obtained with Moller-Plesset perturbation theory and with model potential are quite close to each other and also close to experimental data.Comment: 33 pages including 10 figure

Clathrate hydrates — efficient and clean energy resource

Clathrate hydrates are icelike structures in which water molecules form cavities enclathrating many possible types of guest molecules. Among most important representatives of this group of solid structures are methane and carbon dioxide clathrate hydrates. The first one is widely present in Nature and in the future will serve as an energy resource. Carbon dioxide clathrate hydrate may on the other hand serve as a storage reservoir for this green house gas providing cheap way to lower its emission to atmosphere. Those are just two of many more important issues that catalyse growing interest of scientific world in clathrate hydrates. Characterisation of their properties is crucial to develop technologies, that will enable us to utilize their manifold possible applications. During this presentation I will discuss some of my investigations concerning NMR properties of clathrate hydrates