Scalable Software Services for Life Science

DALTON Use Case Scenarios

Determination of the small proteins structure from first principles.

Contributed by Zilvinas Rinkevicius

Objective: Accurate prediction electronic and geometrical structure of small proteins from first principles for refinement of the x-ray crystallography results.

Description: DALTON program is capable of performing geometry optimization of large organic molecules and small proteins in linear scaling fashion at the pure density functional theory level. Recently researcher at University of Oslo (Norway) predicted structure of collagenlike peptide, tintin protein I27 domain and crambin protein using this approach. The calculations have been carried out using BP86 functional and def2-SV(P) basis set and obtained results indicates that the density functional theory are not only useful tool for refining hydrogen atoms positions in protein, but also of the protein structure around disulfide bonds.

Reference: S. Reine, A. Krapp,M. F. Iozzi, V. Bakken, T. Helgaker, F. Pawłowski,and P. Sałek, “An efficient density-functional-theory force evaluation for large molecular systems”, J. Chem. Phys., vol. 133, 044102 (2010) [doi:10.1063/1.3459061]

Modeling of absorption spectra of small dyes in protein environment.

Objective: Determine the change of the optical absorption spectra of the small dyes upon binding to protein using hybrid density functional theory/molecular mechanics approach.

Description: QM/MM module in DALTON program is capable of computing various optical properties of molecules in solution and protein environments using the partition of the system into ʻsmallʼ quantum and ʻlargeʼ classical regions, where first region is described by density functional theory or coupled cluster method and the second region is described by classical force. Recently researchers at Royal Institute of Technology (Sweden) investigated one- and two-photon absorption spectra of Nile Red, which is frequently used in fluorescence bio-imaging applications, in water and bound to beta-lacto globulin protein and determine optimal laser excitation wave length for selective excitation of only protein bound dye molecules.

Reference: . N. Murugan, J. Kongsted, Z. Rinkevicius, and H. Ågren, “Structure and Color Modeling of optical probes within proteins. A case study of nile red in beta-lacto globulin”, submitted to Phys. Chem. Chem. Phys.

Prediction of EPR spin Hamiltonian parameters of spin labels bound to proteins.

Objective: Evaluation of the EPR spin Hamiltonian parameters of fluorescent spin labels absorption bound to insulin beta sheet.

Description: QM/MM module in DALTON program is capable of computing electronic    g- tensors and hyperfine coupling constants of various radicals and transition metal complexes in solution and protein environments using the partition of the system into ʻsmallʼ quantum and ʻlargeʼ classical regions, where first region is described by density functional theory or coupled cluster method and the second region is described by classical force. Recently researchers at Royal Institute of Technology (Sweden) investigated fluorescent spin label bound to model of insulin beta sheet and determine itʼs EPR parameters of the spin label. Based on these results chemical modifications of the spin label have been proposed in order to enhance spin label applicability to EPR imaging of fibrils in brain tissue caused by Alzheimerʼs disease.

Reference: X. Li,    Z. Rinkevicius, N. Murugan, J. Kongsted, Z. Rinkevicius, M. Lindgren, and H. Ågren, “Fluorescent spin labels in protein environment”, in preparation.