22 research outputs found
Plus- and Minus-End Directed Microtubule Motors Bind Simultaneously to Herpes Simplex Virus Capsids Using Different Inner Tegument Structures
Many viruses depend on host microtubule motors to reach their destined intracellular location. Viral particles of neurotropic alphaherpesviruses such as herpes simplex virus 1 (HSV1) show bidirectional transport towards the cell center as well as the periphery, indicating that they utilize microtubule motors of opposing directionality. To understand the mechanisms of specific motor recruitment, it is necessary to characterize the molecular composition of such motile viral structures. We have generated HSV1 capsids with different surface features without impairing their overall architecture, and show that in a mammalian cell-free system the microtubule motors dynein and kinesin-1 and the dynein cofactor dynactin could interact directly with capsids independent of other host factors. The capsid composition and surface was analyzed with respect to 23 structural proteins that are potentially exposed to the cytosol during virus assembly or cell entry. Many of these proteins belong to the tegument, the hallmark of all herpesviruses located between the capsid and the viral envelope. Using immunoblots, quantitative mass spectrometry and quantitative immunoelectron microscopy, we show that capsids exposing inner tegument proteins such as pUS3, pUL36, pUL37, ICP0, pUL14, pUL16, and pUL21 recruited dynein, dynactin, kinesin-1 and kinesin-2. In contrast, neither untegumented capsids exposing VP5, VP26, pUL17 and pUL25 nor capsids covered by outer tegument proteins such as vhs, pUL11, ICP4, ICP34.5, VP11/12, VP13/14, VP16, VP22 or pUS11 bound microtubule motors. Our data suggest that HSV1 uses different structural features of the inner tegument to recruit dynein or kinesin-1. Individual capsids simultaneously accommodated motors of opposing directionality as well as several copies of the same motor. Thus, these associated motors either engage in a tug-of-war or their activities are coordinately regulated to achieve net transport either to the nucleus during cell entry or to cytoplasmic membranes for envelopment during assembly
Berechnung des Circulardichroismus von Ribonuclease und kleineren organischen Molekülen unterschiedlicher Flexibilität
Berechnung des Circulardichroismus von Ribonuclease und kleineren organischen Molekülen unterschiedlicher Flexibilität
Semiempirical Quantum Chemical Calculations Accelerated on a Hybrid Multicore CPU–GPU Computing Platform
In this work, we demonstrate that semiempirical quantum
chemical
calculations can be accelerated significantly by leveraging the graphics
processing unit (GPU) as a coprocessor on a hybrid multicore CPU–GPU
computing platform. Semiempirical calculations using the MNDO, AM1,
PM3, OM1, OM2, and OM3 model Hamiltonians were systematically profiled
for three types of test systems (fullerenes, water clusters, and solvated
crambin) to identify the most time-consuming sections of the code.
The corresponding routines were ported to the GPU and optimized employing
both existing library functions and a GPU kernel that carries out
a sequence of noniterative Jacobi transformations during pseudodiagonalization.
The overall computation times for single-point energy calculations
and geometry optimizations of large molecules were reduced by one
order of magnitude for all methods, as compared to runs on a single
CPU core
Semiempirical Quantum-Chemical Orthogonalization-Corrected Methods: Benchmarks of Electronically Excited States
The
semiempirical orthogonalization-corrected OMx methods have
recently been shown to perform well in extensive ground-state benchmarks.
They can also be applied to the computation of electronically excited
states when combined with a suitable multireference configuration
interaction (MRCI) treatment. We report on a comprehensive evaluation
of the performance of the OMx/MRCI methods for electronically excited
states. The present benchmarks cover vertical excitation energies,
excited-state equilibrium geometries (including an analysis of significant
changes between ground- and excited-state geometries), minimum-energy
conical intersections, ground- and excited-state zero-point vibrational
energies, and 0–0 transition energies for a total of 520 molecular
structures and 412 excited states. For comparison, we evaluate the
TDDFT/B3LYP method for all benchmark sets, and the CC2, MRCISD, and
CASPT2 methods for some of them. We find that the current OMx/MRCI
methods perform reasonably well for many of the excited-state properties.
However, in comparison to the first-principles methods, there are
also a number of shortcomings that should be addressed in future developments