title: Role of structural water for prediction of cation binding sites in apoproteins.
abstract: Structures of many metal-binding proteins are often obtained without structural cations in their apoprotein forms. Missing cation coordinates are usually updated from structural templates constructed from many holoprotein structures. Such templates usually do not include structural water, the important contributor to the ion binding energy. Structural templates are also inconvenient for taking into account structural modifications around the binding site at apo-/holo- transitions. An approach based upon statistical potentials readily takes into account structural modifications associated with binding as well as contribution of structural water molecules. Here, we construct a set of statistical potentials for Mg2+, Ca2+, and Zn2+contacting with protein atoms of a different type or structural water oxygens. Each type of the cations tends to form tight contacts with protein atoms of specific types. Structural water contributes relatively more into the binding pseudo-energy of Mg2+and Ca2+than of Zn2+. We have developed PIONCA (Protein-Ion Calculator), a fast CUDA GPGPU-based algorithm that predicts ion-binding sites in apoproteins. Comparative tests demonstrate that PIONCA outperforms most of the tools based on structural templates or docking. Our software can be also used for locating bound cations in holoprotein structures with missing cation heteroatoms. PIONCA is equipped with an interactive web interface based upon JSmol.
authors.affiliation: a Department of Computational Systems Biology , Vavilov Institute of General Genetics , 3 Gubkina st., Moscow 119991 , Russian Federation.
authors.forename: L A
authors.initials: LA
authors.lastname: Uroshlev
authors.affiliation: a Department of Computational Systems Biology , Vavilov Institute of General Genetics , 3 Gubkina st., Moscow 119991 , Russian Federation.|b Engelhardt Institute of Molecular Biology , Russian Academy of Sciences , 32 Vavilova st., Moscow 119991 , Russian Federation.
authors.forename: I V
authors.initials: IV
authors.lastname: Kulakovskiy
authors.affiliation: b Engelhardt Institute of Molecular Biology , Russian Academy of Sciences , 32 Vavilova st., Moscow 119991 , Russian Federation.
authors.forename: N G
authors.initials: NG
authors.lastname: Esipova
authors.affiliation: b Engelhardt Institute of Molecular Biology , Russian Academy of Sciences , 32 Vavilova st., Moscow 119991 , Russian Federation.
authors.forename: V G
authors.initials: VG
authors.lastname: Tumanyan
authors.affiliation: a Department of Computational Systems Biology , Vavilov Institute of General Genetics , 3 Gubkina st., Moscow 119991 , Russian Federation.
authors.forename: S V
authors.initials: SV
authors.lastname: Rahmanov
authors.affiliation: a Department of Computational Systems Biology , Vavilov Institute of General Genetics , 3 Gubkina st., Moscow 119991 , Russian Federation.|b Engelhardt Institute of Molecular Biology , Russian Academy of Sciences , 32 Vavilova st., Moscow 119991 , Russian Federation.|c State Research Institute of Genetics and Selection of Industrial Microorganisms , GosNIIGenetika , 1st Dorozhniy proezd 1, Moscow 117545 , Russian Federation.|d Department of Medical and Biological Physics , Moscow Institute of Physics and Technology , 9 Institutskiy per., Moscow 141700 , Russian Federation.
authors.forename: V J
authors.initials: VJ
authors.lastname: Makeev
mesh_terms: D000465:Algorithms; D001059:Apoproteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002412:Cations / Q000737:chemistry* / Q000378:metabolism; D019295:Computational Biology / Q000379:methods; D008670:Metals / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D012984:Software; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
chemical_list: D001059:Apoproteins; D002412:Cations; D008670:Metals; D014867:Water
keywords: Ca2+; Mg2+; PIONCA; Zn2+; statistical potential; structural cations; structural water