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The Hindu
2 days ago
- Science
- The Hindu
BioEmu AI reveals protein choreography in biological conditions
Proteins aren't rigid sculptures. They twist, flex, and sometimes unravel — movements essential to understanding their function. Some proteins, like enzymes, open like clamshells to grab molecules. Others such as signalling proteins shift shape to control cell processes. Still others briefly reveal hidden gaps where drugs can bind. Artificial intelligence (AI) tools like AlphaFold have made structure prediction routine, but they typically yield just one stable form, a single frame from what is really a moving picture. A new deep learning system called BioEmu, developed by Microsoft and researchers at Rice University in the US and Freie Universität in Germany, predicts the full range of shapes a protein naturally explores under biological conditions. Known as the equilibrium ensemble, it allows high-resolution protein flexibility modelling at scale, unlike slower, more classical approaches. Described in Science, BioEmu is faster and cheaper, enabling large-scale predictions of protein function. To understand BioEmu's significance, it helps to see what it's up against. The gold standard for modeling protein flexibility is molecular dynamics (MD), which tracks atomic movements at millionths of a billionth of a second using tools like GROMACS or Anton. Despite its ultrafine resolution and accuracy, MD is slow and costly. Simulating motions over microseconds or milliseconds can take tens of thousands of GPU-hours, even on supercomputers. BioEmu sidesteps this bottleneck by relying on an AI diffusion model. To train BioEmu, researchers first fed it real protein structures, from millions of AlphaFold-predicted assemblies, 200 milliseconds of MD simulations spanning thousands of proteins, and half a million mutant sequences from experimental stability measurements. It's like dropping a sugar cube into a glass of water: the original structure, clear and defined, is gradually dissolved. BioEmu's real task is to learn how to run that process in reverse: from noise to a sugar cube. Once trained, it can generate thousands of plausible protein conformations from scratch. BioEmu excelled at benchmarks. It captured large shape changes in enzymes, local unfolding that switches proteins on or off, and fleeting cryptic pockets, temporary crevices that can serve as drug docking sites, like in the cancer-linked protein Ras. It predicted 83% of large shifts and 70-81% of small changes accurately, including open and closed forms of a vital enzyme called adenylate kinase. It also handled hard to predict proteins that don't have a fixed 3D structure and how mutations affect protein stability. Fast but not fully detailed While MD simulates how proteins move over time, including interactions with water and drugs, BioEmu quickly generates snapshots of all the stable shapes a protein is likely to adopt. It can produce thousands of these structures in minutes to hours on a single GPU. But it can't show how a process unfolds. 'If a researcher wants to understand how a drug reaches a hidden binding site, MD can reveal the step-by-step pathway,' says Kalairasan Ponnuswamy, bioinformatician and assistant professor at SRM Institute of Science and Technology. 'BioEmu shows the final shapes, not how the protein gets there.' MD also handles temperature shifts, membranes, and other conditions that BioEmu's static predictions can't yet model. BioEmu also can't model cell walls, drug molecules, pH changes or show prediction reliability like AlphaFold. It's also limited to single chains and can't model how proteins interact, a key part of most biological processes and drug targets. 'It's better seen as a hypothesis-generating tool than a source of final conclusions,' says Ponnuswamy. As the system grows to handle more complex proteins and chemical interactions, researchers may still need experiments or older simulation methods to validate what it proposes. Still, the conceptual advance is clear. If AlphaFold provided the protein world's blueprint, BioEmu sketches its choreography. By capturing flexibility quickly across thousands of proteins, it enables large-scale drug discovery and function studies with fewer resource constraints, Ponnuswamy notes: 'Tasks that took weeks will now take hours.' He does however emphasise the need for proper training and skill-set acquisition. 'Future scientists will not only need a deep grounding in physics and chemistry, they'll also need fluency in machine learning and physical modelling to unlock the true potential of such hybrid approaches.' The researchers see BioEmu and MD as complementary tools. BioEmu can quickly generate a range of plausible conformations, which MD can then explore in detail. This hybrid approach could greatly reduce simulation time while preserving fidelity. Anirban Mukhopadhyay is a geneticist by training and science communicator from Delhi.
Yahoo
27-04-2025
- Business
- Yahoo
Intel: Now Or Never
After a series of missteps over the years, Intel, once the market leader and a sign of innovation, lost its position. It is now facing substantial financial pressure as losses pile up. However, its last move, given the market's circumstances, could change direction and save it, putting it in a formidable position. Intel's revenue is a cause of concern as in 2022, 2023, and 2024, it had declines in sales of 20.2%, 14%, and 2.1%, respectively. Although the rate of decline is decreasing as well, this could get back to double-digit levels if the company does not stop losing market share. In the profitability side, the company went from a mid-30% net income range in 2019 to a 7.2% loss in 2024. This reveals difficulties in pricing its products competitively and a massive capital expenditure related to manufacturing expansion. Free cash flow turned negative in 2022, and since then, the loss margin has been in the high 20s Intel's product line shows signs of revitalization, with processors rivaling AMD's gaming. This shows a much-needed technical upgrade from past versions, where they consistently fell behind AMD. On the server side, performance benchmarks show that the new Granite Rapids platform outperforms the competition. As presented by Phorinix in the following tests: GROMACS is a molecular dynamics package mainly designed to simulate proteins, lipids, and nucleic acids. Granite Rapids GROMACS performance (Source Phoronix) OpenFOAM is a C++ toolbox for developing customized numerical solvers and pre-/post-processing utilities for solving continuum mechanics problems, most prominently including computational fluid dynamics. Granite Rapids OpenFOAM performance (Source Phoronix) NAS Parallel LU The NAS Parallel LU is a Lower-Uppersymmetric Gauss-Seidel kernel that requires a good memory and compute bandwidth balance. The discrete GPU efforts are yielding products with reasonable performance, getting close to AMD, and a price advantage, with the best price per FPS. However, competition against NVIDIA is yet to be seen, as the ecosystem for NVIDIA GPUs is now the most robust. Warning! GuruFocus has detected 7 Warning Signs with INTC. With the new tariffs implemented and the ever-increasing tensions, domestic production of high-performance chips is growing in importance. Taiwan, where TSMC is located, has been constantly under the risk of annexation by China and will be one of the first places to be invaded in a case of escalation. This is a significant security threat for the US, which depends on its production. Companies like Apple, NVIDIA, AMD, Broadcom, and Qualcomm all depend on TSMC's manufacturing power. To address this problem, the US government has created the CHIPS Act, with $39 billion directed to semiconductor manufacturing projects, which signals interest in the matter. Due to the industry's capital-intensive nature -Intel's capex is already over $25 billioneven more funds could be approved. Intel is leading the charge on domestic production. While AMD, Apple, and NVIDIA will use TSMC's plants in the US, Intel is building its own. This reduces costs, keeps earnings local, and avoids the risk of TSMC being overloaded with orders or plagiarizing technology in the case of falling into China's control, making Intel an ideal candidate for government aid. The cornerstone of Intel's turnaround is its IDM 2.0 strategy, which aims to restore manufacturing leadership while simultaneously building a foundry services business. This dual approach requires unprecedented capital expenditure, with the company moving from $16 billion in 2019 to over $25 billion in 2022 and 2023. If Intel's plans work out. It'll be the only PC/server company to develop and produce its chips in the US at scale, beating (at least for a moment) AMD in the long-standing battle between the two. Investors seem to be overlooking this possibility, as Intel is trading below AMD's and peer numbers. Intel trades at relatively undemanding multiples compared to its semiconductor peers, with a P/S ratio of 1.54 versus the industry average of 2.38 and a 4.39 for AMD. This discount reflects the current sentiment about the company since its missteps. The valuation incorporates significant skepticism regarding Intel's ability to restore technology leadership and manufacturing competitiveness. Under these circumstances, if the company executes its roadmap successfully and takes back its place and market share, there is substantial upside potential from current levels. GuruFocus's valuation of the company seems to consider this and serves as a point of reference for the company's fair price. Intel's balance sheet has deteriorated as the company funds its manufacturing transformation. Long-term debt increased substantially, from $33 billion in 2020 to over $46 billion by 2024. The company's decision to cut its dividend by 66% in early 2023 signaled the financial pressure created by its capital-intensive strategy. The CEO of TSMC has seen the risk of being replaced and now wants to invest $100 billion in US soil to manufacture its technology there. However, the deal needs to be approved by the Taiwanese government, and fears of losing the protective effect of the semiconductor business might disincentivize the approval. This movement can be seen as TSMC trying to flee Taiwan, leaving behind the risks of annexation by China and an unprotected country. Hence, the approval is unlikely when national interests weigh more. Intel faces intensifying competition across its business units: Data centers: AMD has leveraged TSMC's manufacturing advantages to deliver superior performance per watt, increasing its server market share from single digits to 33% by Q1Y2024. Furthermore, since its unit market share is 23.6%, that means AMD chips command a higher price per unit. Nvidia with its GPUs being more efficient for AI applications, has completely dominated the AI accelerator market, with Intel's efforts in this high-growth segment yielding minimal traction. Client computing: Apple moved away from Intel to create its own processors, yielding high performance and never-before-seen battery life. At the same time, AMD's chips are becoming the go-to for Windows machines. Intel represents a high-risk, potentially high-reward investment proposition. With current levels of instability at an all-time high across most industries, the stock price presents a strong appeal. The current trade war can be a tailwind for the company and one of the few to come out of this with a positive experience. However, this position should be sized conservatively within a diversified portfolio, acknowledging the substantial execution risks. Intel's plans will require years to materialize, testing investor patience. Yet for those who can maintain a truly long-term perspective, the company's combination of engineering talent, manufacturing scale, and governmental support provides a foundation for potential value creation that the market may be underappreciating. This article first appeared on GuruFocus. Sign in to access your portfolio
Yahoo
27-04-2025
- Business
- Yahoo
Intel: Now Or Never
After a series of missteps over the years, Intel, once the market leader and a sign of innovation, lost its position. It is now facing substantial financial pressure as losses pile up. However, its last move, given the market's circumstances, could change direction and save it, putting it in a formidable position. Intel's revenue is a cause of concern as in 2022, 2023, and 2024, it had declines in sales of 20.2%, 14%, and 2.1%, respectively. Although the rate of decline is decreasing as well, this could get back to double-digit levels if the company does not stop losing market share. In the profitability side, the company went from a mid-30% net income range in 2019 to a 7.2% loss in 2024. This reveals difficulties in pricing its products competitively and a massive capital expenditure related to manufacturing expansion. Free cash flow turned negative in 2022, and since then, the loss margin has been in the high 20s Intel's product line shows signs of revitalization, with processors rivaling AMD's gaming. This shows a much-needed technical upgrade from past versions, where they consistently fell behind AMD. On the server side, performance benchmarks show that the new Granite Rapids platform outperforms the competition. As presented by Phorinix in the following tests: GROMACS is a molecular dynamics package mainly designed to simulate proteins, lipids, and nucleic acids. Granite Rapids GROMACS performance (Source Phoronix) OpenFOAM is a C++ toolbox for developing customized numerical solvers and pre-/post-processing utilities for solving continuum mechanics problems, most prominently including computational fluid dynamics. Granite Rapids OpenFOAM performance (Source Phoronix) NAS Parallel LU The NAS Parallel LU is a Lower-Uppersymmetric Gauss-Seidel kernel that requires a good memory and compute bandwidth balance. The discrete GPU efforts are yielding products with reasonable performance, getting close to AMD, and a price advantage, with the best price per FPS. However, competition against NVIDIA is yet to be seen, as the ecosystem for NVIDIA GPUs is now the most robust. Warning! GuruFocus has detected 7 Warning Signs with INTC. With the new tariffs implemented and the ever-increasing tensions, domestic production of high-performance chips is growing in importance. Taiwan, where TSMC is located, has been constantly under the risk of annexation by China and will be one of the first places to be invaded in a case of escalation. This is a significant security threat for the US, which depends on its production. Companies like Apple, NVIDIA, AMD, Broadcom, and Qualcomm all depend on TSMC's manufacturing power. To address this problem, the US government has created the CHIPS Act, with $39 billion directed to semiconductor manufacturing projects, which signals interest in the matter. Due to the industry's capital-intensive nature -Intel's capex is already over $25 billioneven more funds could be approved. Intel is leading the charge on domestic production. While AMD, Apple, and NVIDIA will use TSMC's plants in the US, Intel is building its own. This reduces costs, keeps earnings local, and avoids the risk of TSMC being overloaded with orders or plagiarizing technology in the case of falling into China's control, making Intel an ideal candidate for government aid. The cornerstone of Intel's turnaround is its IDM 2.0 strategy, which aims to restore manufacturing leadership while simultaneously building a foundry services business. This dual approach requires unprecedented capital expenditure, with the company moving from $16 billion in 2019 to over $25 billion in 2022 and 2023. If Intel's plans work out. It'll be the only PC/server company to develop and produce its chips in the US at scale, beating (at least for a moment) AMD in the long-standing battle between the two. Investors seem to be overlooking this possibility, as Intel is trading below AMD's and peer numbers. Intel trades at relatively undemanding multiples compared to its semiconductor peers, with a P/S ratio of 1.54 versus the industry average of 2.38 and a 4.39 for AMD. This discount reflects the current sentiment about the company since its missteps. The valuation incorporates significant skepticism regarding Intel's ability to restore technology leadership and manufacturing competitiveness. Under these circumstances, if the company executes its roadmap successfully and takes back its place and market share, there is substantial upside potential from current levels. GuruFocus's valuation of the company seems to consider this and serves as a point of reference for the company's fair price. Intel's balance sheet has deteriorated as the company funds its manufacturing transformation. Long-term debt increased substantially, from $33 billion in 2020 to over $46 billion by 2024. The company's decision to cut its dividend by 66% in early 2023 signaled the financial pressure created by its capital-intensive strategy. The CEO of TSMC has seen the risk of being replaced and now wants to invest $100 billion in US soil to manufacture its technology there. However, the deal needs to be approved by the Taiwanese government, and fears of losing the protective effect of the semiconductor business might disincentivize the approval. This movement can be seen as TSMC trying to flee Taiwan, leaving behind the risks of annexation by China and an unprotected country. Hence, the approval is unlikely when national interests weigh more. Intel faces intensifying competition across its business units: Data centers: AMD has leveraged TSMC's manufacturing advantages to deliver superior performance per watt, increasing its server market share from single digits to 33% by Q1Y2024. Furthermore, since its unit market share is 23.6%, that means AMD chips command a higher price per unit. Nvidia with its GPUs being more efficient for AI applications, has completely dominated the AI accelerator market, with Intel's efforts in this high-growth segment yielding minimal traction. Client computing: Apple moved away from Intel to create its own processors, yielding high performance and never-before-seen battery life. At the same time, AMD's chips are becoming the go-to for Windows machines. Intel represents a high-risk, potentially high-reward investment proposition. With current levels of instability at an all-time high across most industries, the stock price presents a strong appeal. The current trade war can be a tailwind for the company and one of the few to come out of this with a positive experience. However, this position should be sized conservatively within a diversified portfolio, acknowledging the substantial execution risks. Intel's plans will require years to materialize, testing investor patience. Yet for those who can maintain a truly long-term perspective, the company's combination of engineering talent, manufacturing scale, and governmental support provides a foundation for potential value creation that the market may be underappreciating. This article first appeared on GuruFocus. Sign in to access your portfolio
