| 1. |
- Aqvist, Johan, et al.
(författare)
-
Bridging the gap between ribosome structure and biochemistry by mechanistic computations
- 2012
-
Ingår i: Current opinion in structural biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; 22:6, s. 815-823
-
Tidskriftsartikel (refereegranskat)abstract
- The wealth of structural and biochemical data now available for protein synthesis on the ribosome presents major new challenges for computational biochemistry. Apart from technical difficulties in modeling ribosome systems, the complexity of the overall translation cycle with a multitude of different kinetic steps presents a formidable problem for computational efforts where we have only seen the beginning. However, a range of methodologies including molecular dynamics simulations, free energy calculations, molecular docking and quantum chemical approaches have already been put to work with promising results. In particular, the combined efforts of structural biology, biochemistry, kinetics and computational modeling can lead towards a quantitative structure-based description of translation.
|
|
| 2. |
- Azinas, Stavros, et al.
(författare)
-
Cryo-EM uniqueness in structure determination of macromolecular complexes : A selected structural anthology
- 2023
-
Ingår i: Current opinion in structural biology. - 0959-440X .- 1879-033X. ; 81
-
Tidskriftsartikel (refereegranskat)abstract
- Cryogenic electron microscopy (cryo-EM) has become in the past 10 years one of the major tools for the structure determination of proteins. Nowadays, the structure prediction field is experiencing the same revolution and, using AlphaFold2, it is possible to have high-confidence atomic models for virtually any polypeptide chain, smaller than 4000 amino acids, in a simple click. Even in a scenario where all polypeptide chain folding were to be known, cryo-EM retains specific characteristics that make it a unique tool for the structure determination of macromolecular complexes. Using cryo-EM, it is possible to obtain near-atomic structures of large and flexible megacomplexes, describe conformational panoramas, and potentially develop a structural proteomic approach from fully ex vivo specimens.
|
|
| 3. |
- Bacic, Luka, et al.
(författare)
-
Recent advances in single-molecule fluorescence microscopy render structural biology dynamic
- 2020
-
Ingår i: Current opinion in structural biology. - LONDON ENGLAND : Elsevier BV. - 0959-440X .- 1879-033X. ; 65, s. 61-68
-
Tidskriftsartikel (refereegranskat)abstract
- Single-molecule fluorescence microscopy has long been appreciated as a powerful tool to study the structural dynamics that enable biological function of macromolecules. Recent years have witnessed the development of more complex single-molecule fluorescence techniques as well as powerful combinations with structural approaches to obtain mechanistic insights into the workings of various molecular machines and protein complexes. In this review, we highlight these developments that together bring us one step closer to a dynamic understanding of biological processes in atomic details.
|
|
| 4. |
- Ban, Nenad, et al.
(författare)
-
A new system for naming ribosomal proteins.
- 2014
-
Ingår i: Current Opinion in Structural Biology. - : Elsevier BV. - 1879-033X .- 0959-440X. ; 24, s. 165-169
-
Tidskriftsartikel (refereegranskat)abstract
- A system for naming ribosomal proteins is described that the authors intend to use in the future. They urge others to adopt it. The objective is to eliminate the confusion caused by the assignment of identical names to ribosomal proteins from different species that are unrelated in structure and function. In the system proposed here, homologous ribosomal proteins are assigned the same name, regardless of species. It is designed so that new names are similar enough to old names to be easily recognized, but are written in a format that unambiguously identifies them as 'new system' names.
|
|
| 5. |
- Bryant, Patrick
(författare)
-
Deep learning for protein complex structure prediction
- 2023
-
Ingår i: Current opinion in structural biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; 79
-
Tidskriftsartikel (refereegranskat)abstract
- Recent developments in the structure prediction of protein complexes have resulted in accuracies rivalling experimental methods in many cases. The high accuracy is mainly observed in dimeric complexes and other problems such as protein disorder and predicting the structure of host-pathogen in-teractions remain. This review highlights the foundation for current accurate structure prediction of protein complexes and possible ways to address the remaining limitations.
|
|
| 6. |
- Carrasco Busturia, David, et al.
(författare)
-
Multiscale biomolecular simulations in the exascale era
- 2024
-
Ingår i: Current opinion in structural biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; 86
-
Tidskriftsartikel (refereegranskat)abstract
- The complexity of biological systems and processes, spanning molecular to macroscopic scales, necessitates the use of multiscale simulations to get a comprehensive understanding. lar dynamics (MD) simulations are crucial for capturing processes beyond the reach of classical MD simulations. The advent of exascale computing offers unprecedented opportunities for scientific exploration, not least within life sciences, where simulations are essential to unravel intricate molecular leveraging the immense computational power of exascale computing requires innovative algorithms and software designs. In this context, we discuss the current status and future prospects of multiscale biomolecular simulations on exascale supercomputers with a focus on QM/MM MD. We highlight our own efforts in developing a versatile and high-performance multiscale simulation framework with the aim of efficient utilization of state-of-the-art supercomputers. We showcase its application in uncovering complex biological mechanisms and its potential for leveraging exascale computing.
|
|
| 7. |
- Carreras-Puigvert, Jordi, et al.
(författare)
-
Artificial intelligence for high content imaging in drug discovery
- 2024
-
Ingår i: Current opinion in structural biology. - : Elsevier. - 0959-440X .- 1879-033X. ; 87
-
Tidskriftsartikel (refereegranskat)abstract
- Artificial intelligence (AI) and high-content imaging (HCI) are contributing to advancements in drug discovery, propelled by the recent progress in deep neural networks. This review highlights AI's role in analysis of HCI data from fixed and livecell imaging, enabling novel label-free and multi-channel fluorescent screening methods, and improving compound profiling. HCI experiments are rapid and cost-effective, facilitating large data set accumulation for AI model training. However, the success of AI in drug discovery also depends on highquality data, reproducible experiments, and robust validation to ensure model performance. Despite challenges like the need for annotated compounds and managing vast image data, AI's potential in phenotypic screening and drug profiling is significant. Future improvements in AI, including increased interpretability and integration of multiple modalities, are expected to solidify AI and HCI's role in drug discovery.
|
|
| 8. |
- Choi, Seong Il, et al.
(författare)
-
A social distancing measure governing the whole proteome
- 2021
-
Ingår i: Current opinion in structural biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; 66, s. 104-111
-
Tidskriftsartikel (refereegranskat)abstract
- Protein folding in vivo has been largely understood in the context of molecular chaperones preventing aggregation of nascent polypeptides in the crowded cellular environment. Nascent chains utilize the crowded environment in favor of productive folding by direct physical connection with cellular macromolecules. The intermolecular repulsive forces by large excluded volume and surface charges of interacting cellular macromolecules, exerting ‘social distancing’ measure among folding intermediates, could play an important role in stabilizing their physically connected polypeptides against aggregation regardless of the physical connection types. The generic intrinsic chaperone activity of cellular macromolecules likely provides a robust cellular environment for the productive protein folding and solubility maintenance at the whole proteome level.
|
|
| 9. |
- Cortina, George A., et al.
(författare)
-
Predicting allostery and microbial drug resistance with molecular simulations
- 2018
-
Ingår i: Current opinion in structural biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; 52, s. 80-86
-
Tidskriftsartikel (refereegranskat)abstract
- Beta-lactamase enzymes mediate the most common forms of gram-negative antibiotic resistance affecting clinical treatment. They also constitute an excellent model system for the difficult problem of understanding how allosteric mutations can augment catalytic activity of already-competent enzymes. Multiple allosteric mutations have been identified that alter catalytic activity or drug-resistance spectrum in class A beta lactamases, but predicting these in advance continues to be challenging. Here, we review computational techniques based on structure and/or molecular simulation to predict such mutations. Structure-based techniques have been particularly helpful in developing graph algorithms for analyzing critical residues in beta-lactamase function, while classical molecular simulation has recently shown the ability to prospectively predict allosteric mutations increasing beta-lactamase activity and drug resistance. These will ultimately achieve the greatest power when combined with simulation methods that model reactive chemistry to calculate activation free energies directly.
|
|
| 10. |
- Daley, Daniel O
(författare)
-
The assembly of membrane proteins into complexes
- 2008
-
Ingår i: Current opinion in structural biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; 18:4, s. 420-4
-
Tidskriftsartikel (refereegranskat)abstract
- Protein complexes are a fundamental aspect of life in a membrane. It is therefore important to understand which proteins are assembled, and how the process of assembly is coordinated. To this end, a number of themes have emerged from the literature in recent years: first, membrane proteins assemble in an ordered, rather than a stochastic manner; second, they require chaperones to prevent unwanted interactions/aggregation; and third, they can be assembled into existing complexes. As these recurrent themes have emerged from studies on disparate complexes, they provide a general framework to understand the assembly of membrane proteins.
|
|
